共查询到20条相似文献,搜索用时 31 毫秒
1.
Tao Wang Hongli Liu Yeshan Chen Wei Liu Jing Yu Gang Wu 《Journal of experimental & clinical cancer research : CR》2009,28(1):160
Background
Epigenetic silencing of tumor suppressor genes associated with promoter methylation is considered to be a hallmark of oncogenesis. RASSF1A is a candidate tumor suppressor gene which was found to be inactivated in many human cancers. Although we have had a prelimilary cognition about the function of RASSF1A, the exact mechanisms about how RASSF1A functions in human cancers were largely unknown. Moreover, the effect of mutated K-Ras gene on the function of RASSF1A is lacking. The aim of this study was to investigate the expression profile and methylation status of RASSF1A gene, and to explore its concrete mechanisms as a tumor suppressor gene in Nasopharyngeal Carcinoma.Methods
We examined the expression profile and methylation status of RASSF1A in two NPC cell lines, 38 primary nasopharyngeal carcinoma and 14 normal nasopharyngeal epithelia using RT-PCR and methylated specific PCR(MSP) respectively. 5-aza-dC was then added to confirm the correlation between hypermethylation status and inactivation of RASSF1A. The NPC cell line CNE-2 was transfected with exogenous pcDNA3.1(+)/RASSF1A plasmid in the presence or absence of mutated K-Ras by liposome-mediated gene transfer method. Flow cytometry was used to examine the effect of RASSF1A on cell cycle modulation and apoptosis. Meanwhile, trypan blue dye exclusion assays was used to detect the effect of RASSF1A transfection alone and the co-transfection of RASSF1A and K-Ras on cell proliferation.Results
Promoter methylation of RASSF1A could be detected in 71.05% (27/38) of NPC samples, but not in normal nasopharyngeal epithelia. RASSF1A expression in NPC primary tumors was lower than that in normal nasopharyngeal epithelial (p < 0.01). Expression of RASSF1A was down-regulated in two NPC cell lines. Loss of RASSF1A expression was greatly restored by the methyltransferase inhibitor 5-aza-dC in CNE-2. Ectopic expression of RASSF1A in CNE-2 could increase the percentage of G0/G1 phase cells (p < 0.01), inhibit cell proliferation and induce apoptosis (p < 0.001). Moreover, activated K-Ras could enhance the growth inhibition effect induced by RASSF1A in CNE-2 cells (p < 0.01).Conclusion
Expression of RASSF1A is down-regulated in NPC due to the hypermethylation of promoter. Exogenous expression of RASSF1A is able to induce growth inhibition effect and apoptosis in tumor cell lines, and this effect could be enhanced by activated K-Ras. 相似文献2.
3.
Carmen Bala?�� Cristina Carrato Jos�� Luis Ram��rez Andr��s Felipe Cardona Mireia Berdiel Jos�� Javier S��nchez Miquel Tar��n Cristina Hostalot Eva Musulen Aurelio Ariza Rafael Rosell 《Clinical & translational oncology》2011,13(9):677-685
Introduction
Methylation of the promoter of the MGMT gene and MGMT protein expression are recognized as predictive markers for response to alkylating chemotherapy in glioblastoma (GB).Material and methods
We have assessed MGMT methylation with the methylation-specific polymerase chain reaction (MSP) in tumor samples from 70 GB patients and in serum samples from 37 of these patients. We have also assessed MGMT protein expression by immunohistochemical (IHC) analysis in tissue samples from 63 of these patients.Results
We found concordance between MGMT methylation status in tissue and serum (Cohen??s Kappa = 0.586; p<0.0001). MSP for detection of non-methylated MGMT promoter in serum showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation test showed a low specificity (8.9%). Patients whose MGMT promoter was methylated in tissue attained longer progression-free and overall survival. In the multivariate analysis, serum MGMT promoter methylation emerged as an independent factor for longer progression-free and overall survival.Conclusion
Serum-based MGMT methylation analysis offers a promising alternative to tumor-based MGMT analysis in cases where tissue samples are unavailable. 相似文献4.
L. Li Y. Shen M. Wang D. Tang Y. Luo W. Jiao Z. Wang R. Yang K. Tian 《Clinical & translational oncology》2014,16(6):581-589
Background
Recent diagnostic procedure advances have greatly improved early lung cancer detection. However, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their application. There is a great need of novel non-invasive biomarkers for early lung cancer diagnosis. In the present study, we intend to determine whether the blood signatures of p14ARF promoter methylation are suitable for early detection of lung cancer.Methods
The study aimed to assess the probability of p14ARF promoter methylation in plasma samples to detect early lung cancer using nested methylation-specific PCR in the training set consisted of tumor tissues and paired blood. Besides, we were further to discuss the difference in time to progression between methylation and unmethylation of p14ARF promoter using univariate and multivariate analysis.Results
The methylation of p14ARF promoter was detected in 33.6 % of tumor tissues, and 12.1 and 25.2 % in distant-cancer mucosa and matched plasma, respectively, and our study has also demonstrated the positive correlation between them by Pearson’s test (r = 0.300). The tumor-free survival time of the unmethylation of p14ARF promoter is significantly longer than that of the methylation of p14ARF promoter in tumor tissues (χ 2 = 7.149, P = 0.008).Conclusion
The methylation of p14ARF promoter in plasma samples has strong potential as a novel non-invasive biomarker for early detection of lung cancer, and the methylation of p14ARF promoter was considered as prognostic factor in our study. 相似文献5.
Lars Henrik Jensen Anders Aamann Rasmussen Lene Byriel Hidekazu Kuramochi Dorthe Gylling Crüger Jan Lindebjerg Peter V. Danenberg Anders Jakobsen Kathleen Danenberg 《Cellular oncology (Dordrecht)》2013,36(5):411-419
Background
In colorectal cancer MLH1 deficiency causes microsatellite instability, which is relevant for the patient’s prognosis and treatment, and its putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter hypermethylation or by hereditary mutations as seen in Lynch Syndrome. The aim of this study was to determine in detail how DNA methylation regulates MLH1 expression and impacts clinical management.Methods
Colorectal cancer samples were collected from 210 patients. The laboratory methods used to study these samples included methylation specific multiplex ligation-dependent probe amplification (MS-MLPA), real-time quantitative PCR (qPCR), and immunohistochemistry (IHC).Results
We found that the MLH1 mRNA and protein expression levels were highly related. MS-MLPA was successful in tumors from 195 patients. In these tumors, hypermethylation was observed in promoter regions A (n?=?57), B (n?=?30), C (n?=?28), and D (n?=?47), and in intron 1 (n?=?25). The promoter region C and intron 1 methylation levels were found to be excellently suited for discriminating between low and high gene expression levels, whereas those of promoter regions A, B and D were less specific. Hypermethylation in any region (n?=?77) served as an independent prognostic factor (hazard ratio 0.56, 95 % confidence interval 0.36–0.89, p?=?0.01).Conclusions
MLH1 inactivation through hypermethylation was found to be related to improved survival. Hypermethylation in promoter region C and intron 1 served as the most specific markers for this inactivation. 相似文献6.
Chiaki Banzai Koji Nishino Jinhua Quan Kosuke Yoshihara Masayuki Sekine Tetsuro Yahata Kenichi Tanaka 《International journal of clinical oncology / Japan Society of Clinical Oncology》2014,19(1):127-132
Background and objectives
Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of human cancer. This study explored the relationship between promoter methylation and inactivation of the DAPK1, FHIT, MGMT, and CDKN2A genes in cervical cancer.Methods
The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens. The correlation of promoter methylation with the clinicopathological features of cervical cancer was analyzed. The expressions of DAPK1, FHIT, MGMT, and CDKN2A were detected by measuring relative mRNA levels.Results
The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A in cervical cancer vs. intraepithelial neoplasia vs. normal cervical tissue was 75.5 vs. 31.8 vs. 4.2 % (p < 0.0001), 66.0 vs. 59.1 vs. 25.0 % (p = 0.0033), 34.0 vs. 27.3 vs. 20.8 % (p = 0.76), and 17.0 vs. 31.8 vs. 8.3 % (p = 0.11), respectively. The methylation of the promoter region significantly decreased the expression of only DAPK1 (p = 0.03). The methylation rate of the DAPK1 gene promoter was significantly higher in cervical cancer tissues than in cervical intraepithelial neoplasia and normal cervical tissues.Conclusion
Promoter methylation may therefore lead to the inactivation of the DAPK1 gene, and may be related to the progression of cervical oncogenesis. 相似文献7.
Tarique N. Hasan B. Leena Grace Gowhar Shafi Rabbani Syed 《Clinical & translational oncology》2013,15(7):555-562
Objective
Breast cancer is the most common cancer and the main cause of cancer morbidity for women worldwide and is manifestation of abnormal genetic as well as epigenetic changes. Therefore, our aim was to study the association of BRCA1 promoter methylation with rs11655505 (c.?2265C/T) variants and gene expression in sporadic breast cancer.Methods
Twenty-nine sporadic breast cancer tissues and 26 normal biopsies were used for this study. Genomic DNA and total RNA were extracted from paraffin-embedded tissue and SNP analysis performed. Methylation status of the BRCA1 promoter region was determined by methylation-specific PCR after sodium bisulfite modification of DNA.Results
Among all clinical–pathological parameters only estrogen receptor –ve and +ve samples were significantly different for methylation status (P = 0.04). The genotypic (CC, CT and TT), allelic frequencies and methylation status had not been found to be significantly different from that of healthy controls (P = 0.67, 0.71 and 0.17, respectively). Similarly, methylated BRCA1 promoter was not found to be significantly different in different genotypes from unmethylated promoters between patients and controls. Interestingly, only heterozygous (CT) genotypes with low and normal expression of BRCA1 were significantly different for the differential expression of BRCA1 compared to controls (P = 0.004). However, in tumor samples decreased expression of gene is associated with methylated state of BRCA1 promoter [OR (95 % CI) = 25.09 (2.17–29.75); P = 0.01].Conclusions
Our data suggest that both single nucleotide variations rs11655505 (c.–2265C/T) and the methylation status of BRCA1 are not associated significantly with the occurrence of sporadic breast cancer in studied population. However, decreased expression of gene is associated with the CT genotypes and the disease. But, in case of tumor samples, an association of methylation of the promoter to the decreased expression of BRCA1 gene suggests the possible role of methylation in gene silencing. 相似文献8.
Xavier Tekpli Vidar Skaug Rita Bæra David H. Phillips Aage Haugen Steen Mollerup 《Cellular oncology (Dordrecht)》2016,39(6):583-589
Purpose
In the past, anomalous estrogen receptor (ER) regulation has been associated with various lung pathologies, but so far its involvement in lung cancer initiation and/or progression has remained unclear. Here, we aimed at assessing in vivo and in vitro ER expression and its possible epigenetic regulation in non-small cell lung cancer (NSCLC) samples and their corresponding normal tissues and cells.Methods
ERα and ERβ gene expression levels were assessed using real time quantitative PCR (RT-qPCR), whereas ERα and ERβ gene promoter methylation levels were assessed using DNA bisulfite conversion followed by pyrosequencing. We included NSCLC (n = 87) and adjacent histologically normal lung tissue samples from lung cancer patients (n = 184), primary normal bronchial epithelial-derived cell cultures (n = 11), immortalized bronchial epithelial-derived cell lines (n = 3) and NSCLC derived cell lines (n = 9).Results
Using RT-qPCR we found significantly lower ERα and ERβ expression levels in the NSCLC tissue samples compared to their normal adjacent tissue samples. These lower ER expression levels were confirmed in vitro using primary normal bronchial epithelial-derived cell cultures, immortalized bronchial epithelial-derived cell lines and NSCLC-derived cell lines. By using this latter panel of cells, we found that ER gene promoter hypermethylation was associated with decreased ER expression. In addition we found that in tumor and normal lung tissues, smoking was associated with decreased ER expression and that normal lung tissues with a low ERβ expression level exhibited increased smoking-related DNA adducts.Conclusions
Taken together, our results indicate that decreased ER expression mediated by DNA methylation may play a role in NSCLC development.9.
Sarah Siddiqui Naseem Akhter S. V. S. Deo N. K. Shukla Syed Akhtar Husain 《Breast cancer (Tokyo, Japan)》2016,23(6):922-931
Background
Epigenetic silencing of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through DNA methylation has been implicated in the pathogenesis of breast cancer. Present study investigates the contribution of PTEN promoter methylation and its associated protein expression in sporadic breast cancer patients from North India.Methods
A total of 360 paired breast carcinoma and adjacent normal tissue samples from 180 sporadic breast cancer patients were included in the present study and examined for PTEN promoter methylation status by methylation-specific polymerase chain reaction. Immunohistochemistry method was used for determining PTEN protein expression. Molecular findings were statistically correlated with various clinicopathological parameters to identify associations of clinical relevance.Results
Presence of PTEN promoter methylation (39.44 %) significantly correlated with its expression downregulation (45.56 %) in breast tumors (P = 0.0001). Furthermore, their interaction with various clinical parameters was evidenced in stratified analysis. Correlation of PTEN promoter methylation with histologically more malignant grade and PTEN expression loss with triple negative tumor status remained significant even after Bonferroni correction (P < 0.003).Conclusions
Results implicate promoter methylation to be a mechanism partially responsible for PTEN silencing in sporadic breast cancer for North Indian women. Besides, methylation and expression loss of PTEN exhibited promising potential as candidate biomarkers of risk assessment in subcategorized breast tumors with critical pathologic parameters.10.
Raman Mehrzad Archana Agarwal Garrey T. Faller Joseph A. Fiore 《Journal of gastrointestinal cancer》2014,45(1):40-47
Introduction
Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stability is one of the main genetic issues in cancer biology which is governed via the different repair systems such as DNA mismatch repair (MMR). A clear correlation between MMR defects and tumor progression has been shown. Beside the genetic mutations, epigenetic changes also have a noticeable role in MMR defects.Methods
Here, we assessed promoter methylation status and the level of hMLH1mRNA expression as the main component of MMR system in 51 GC patients using the methylation-specific PCR and real-time PCR, respectively. Moreover, we performed a promoter methylation study of the E-cadherin gene promoter.Results
It was observed that, 12 out of 39 cases (23.5 %) had hMLH1 overexpression. Hypermethylation of hMLH1 and E-cadherin promoter regions were observed in 25.5 and 36.4 %, respectively. Although, there was no significant correlation between hMLH1 mRNA expression and clinicopathological features, there are significant correlations between E-cadherin promoter methylation and tumor stage (p?=?0.028) and location (p?=?0.025). The rate of hMLH1 promoter methylation in this study was lower than that in the other population, showing the importance of the other mechanisms, in gastric tumorigenesis.Conclusion
The results of this study indicate that DNA repair system is adversely affected by hypermethylation of hMLH1 in a fraction of gastric cancer patients. Additionally, E-cadherin hypermethylation seen in a subset of our gastric cancer patients is consistent with other reports showing correlation with aggressiveness and metastasis of gastric cancer. 相似文献11.
T. Gao B. He Y. Pan L. Gu L. Chen Z. Nie Y. Xu R. Li S. Wang 《Clinical & translational oncology》2014,16(4):410-417
Background
H19 gene has been proved to be essential for human tumor growth which contains CpG rich regions. Imprinted gene expression in many cancers is usually associated with the function of methylation. We performed this study to better understand wether H19 DMR methylation correlates to the progression of esophageal squamous cell carcinoma through IGF2 imprinting pathway.Methods
LOI of IGF2 was detected in 276 samples, which were determined as heterozygote with ApaI polymorphism in exon 9 of IGF2 by PCR–RFLP and RT-PCR–RFLP. Methylation status of H19 DMR in informative samples was analyzed by bisulfite sequencing PCR. IGF2 expression was examined by real-time PCR and IHC.Results
208 ESCC patients were informative for ApaI polymorphism. 92 tumor and 30 normal tissues showed IGF2 LOI. Methylation status of H19 CBS6 was higher in patients with IGF2 LOI compared to patients with IGF2 MOI (p < 0.05). IGF2 expression in patients with IGF2 LOI was higher than patients with IGF2 MOI (p < 0.05) which was correlated with lymph node involvement, neoplastic grade and metastasis (p < 0.05).Conclusions
Our results suggested that H19 CBS6 hypermethylation is related to the LOI of IGF2 which usually leads to an overexpression of IGF2, playing important roles in the occurrence, development as well as metastasis of ESCC. Therefore, H19 CBS6 methylation potentially represents a novel clinically relevant epigenetic marker to identify individuals at increased risk for the occurrence, progression and prognosis of ESCC. 相似文献12.
Wnt signalling in human breast cancer: expression of the putative Wnt inhibitor Dickkopf-3 (DKK3) is frequently suppressed by promoter hypermethylation in mammary tumours 总被引:1,自引:0,他引:1
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Veeck J Bektas N Hartmann A Kristiansen G Heindrichs U Knüchel R Dahl E 《Breast cancer research : BCR》2008,10(5):R82-11
Introduction
Expression of the putative Wnt signalling inhibitor Dickkopf-3 (DKK3) is frequently lost in human cancer tissues because of aberrant 5'-cytosine methylation within the DKK3 gene promoter. Since other Wnt signalling inhibitors have been reported to be targets of epigenetic inactivation in human breast cancer, we questioned if DKK3 expression is also epigenetically silenced during breast carcinogenesis and therefore might contribute to oncogenic Wnt signalling commonly found in this disease.Methods
DKK3 mRNA expression and DKK3 promoter methylation were determined by RT-PCR, realtime PCR and methylation-specific PCR in breast cell lines (n = 9), normal breast tissues (n = 19) and primary breast carcinomas (n = 150), respectively. In vitro DNA demethylation was performed by incubating breast cell lines with 5-aza-2'-deoxycytidine and trichostatin A. DKK3 protein expression was analysed by immunohistochemistry in breast carcinomas (n = 16) and normal breast tissues (n = 8). Methylation data were statistically correlated with clinical patient characteristics. All statistical evaluations were performed with SPSS 14.0 software.Results
DKK3 mRNA was downregulated in 71% (five of seven) of breast cancer cell lines and in 68% of primary breast carcinomas (27 of 40) compared with benign cell lines and normal breast tissues, respectively. A DNA demethylating treatment of breast cell lines resulted in strong induction of DKK3 mRNA expression. In tumourous breast tissues, DKK3 mRNA downregulation was significantly associated with DKK3 promoter methylation (p < 0.001). Of the breast carcinomas, 61% (92 of 150) revealed a methylated DKK3 promoter, whereas 39% (58 of 150) retained an unmethylated promoter. Loss of DKK3 expression in association with DKK3 promoter methylation (p = 0.001) was also confirmed at the protein level (p < 0.001). In bivariate analysis, DKK3 promoter methylation was not associated with investigated clinicopathological parameters except patient age (p = 0.007).Conclusions
DKK3 mRNA expression and consequently DKK3 protein expression become frequently downregulated during human breast cancer development due to aberrant methylation of the DKK3 promoter. Since DKK3 is thought to negatively regulate oncogenic Wnt signalling, DKK3 may be a potential tumour suppressor gene in normal breast tissue. 相似文献13.
14.
R J Shaw M M Omar S Rokadiya F A Kogera D Lowe G L Hall J A Woolgar J Homer T Liloglou J K Field J M Risk 《British journal of cancer》2009,101(1):139-144
Background:
Cytoglobin (Cygb) was first described in 2002 as an intracellular globin of unknown function. We have previously shown the downregulation of cytoglobin as a key event in a familial cancer syndrome of the upper aerodigestive tract.Methods:
Cytoglobin expression and promoter methylation were investigated in sporadic head and neck squamous cell carcinoma (HNSCC) using a cross-section of clinical samples. Additionally, the putative mechanisms of Cygb expression in cancer were explored by subjecting HNSCC cell lines to hypoxic culture conditions and 5-aza-2-deoxycitidine treatment.Results:
In clinically derived HNSCC samples, CYGB mRNA expression showed a striking correlation with tumour hypoxia (measured by HIF1A mRNA expression P=0.013) and consistent associations with histopathological measures of tumour aggression. CYGB expression also showed a marked negative correlation with promoter methylation (P=0.018). In the HNSCC cell lines cultured under hypoxic conditions, a trend of increasing expression of both CYGB and HIF1A with progressive hypoxia was observed. Treatment with 5-aza-2-deoxycitidine dramatically increased CYGB expression in those cell lines with greater baseline promoter methylation.Conclusion
We conclude that the CYGB gene is regulated by both promoter methylation and tumour hypoxia in HNSCC and that increased expression of this gene correlates with clincopathological measures of a tumour''s biological aggression. 相似文献15.
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17.
Chen Xie Vinod Vijay Subhash Arpita Datta Natalia Liem Shi Hui Tan Mei Shi Yeo Woei Loon Tan Vivien Koh Fui Leng Yan Foong Ying Wong Wai Keong Wong Jimmy So Iain Beehuat Tan Nisha Padmanabhan Celestial T. Yap Patrick Tan Liang Kee Goh Wei Peng Yong 《Cellular oncology (Dordrecht)》2016,39(2):175-186
Background
Melanoma-associated antigen (MAGE)-A3 is a member of the family of cancer-testis antigens and has been found to be epigenetically regulated and aberrantly expressed in various cancer types. It has also been found that MAGE-A3 expression may correlate with an aggressive clinical course and with chemo-resistance. The objectives of this study were to assess the relationship between MAGE-A3 promoter methylation and expression and (1) gastric cancer patient survival and (2) its functional consequences in gastric cancer-derived cells.Methods
Samples from two independent gastric cancer cohorts (including matched non-malignant gastric samples) were included in this study. MAGE-A3 methylation and mRNA expression levels were determined by methylation-specific PCR (MSP) and quantitative real-time PCR (qPCR), respectively. MAGE-A3 expression was knocked down in MKN1 gastric cancer-derived cells using miRNAs. In addition, in vitro cell proliferation, colony formation, apoptosis, cell cycle, drug treatment, immunohistochemistry and Western blot assays were performed.Results
Clinical analysis of 223 primary patient-derived samples (ntumor?=?161, nnormal?=?62) showed a significant inverse correlation between MAGE-A3 promoter methylation and expression in the cancer samples (R?=??0.63, p?=?5.99e–19). A lower MAGE-A3 methylation level was found to be associated with a worse patient survival (HR: 1.5, 95 % CI: 1.02–2.37, p?=?0.04). In addition, we found that miRNA-mediated knockdown of MAGE-A3 expression in MKN1 cells caused a reduction in its proliferation and colony forming capacities, respectively. Under stress conditions MAGE-A3 was found to regulate the expression of Bax and p21. MAGE-A3 knock down also led to an increase in Puma and Noxa expression, thus contributing to an enhanced docetaxel sensitivity in the gastric cancer-derived cells.Conclusions
From our results we conclude that MAGE-A3 expression is regulated epigenetically by promoter methylation, and that its expression contributes to gastric cell proliferation and drug sensitivity. This study underscores the potential implications of MAGE-A3 as a therapeutic target and prognostic marker in gastric cancer patients.18.
Olivier Trédan Isabelle Ray-Coquard Gisèle Chvetzoff Paul Rebattu Agathe Bajard Sylvie Chabaud David Pérol Chadi Saba Florent Quiblier Jean-Yves Blay Thomas Bachelot 《BMC cancer》2011,11(1):1-9
Background
DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples.Methods
SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH.Results
A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference.Conclusions
Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples. 相似文献19.
Manika Pal-Bhadra M Janaki Ramaiah T Lakshminarayan Reddy Anita Krishnan SNCVL Pushpavalli K Suresh Babu Ashok K Tiwari J Madhusudana Rao Jhillu S Yadav Utpal Bhadra 《BMC cancer》2012,12(1):1-17
Background
Chrysin and its analogues, belongs to flavonoid family and possess potential anti-tumour activity. The aim of this study is to determine the molecular mechanism by which chrysin controls cell growth and induce apoptosis in A375 cells.Methods
Effect of chrysin and its analogues on cell viability and cell cycle analysis was determined by MTT assay and flowcytometry. A series of Western blots was performed to determine the effect of chrysin on important cell cycle regulatory proteins (Cdk2, cyclin D1, p53, p21, p27). The fluorimetry and calorimetry based assays was conducted for characterization of chrysin as HDAC inhibitor. The changes in histone tail modification such as acetylation and methylation was studied after chrysin treatment was estimated by immuno-fluorescence and western blot analysis. The expression of Bcl-xL, survivin and caspase-3 was estimated in chrysin treated cells. The effect of chrysin on p21 promoter activity was studied by luciferase and ChIP assays.Results
Chrysin cause G1 cell cycle arrest and found to inhibit HDAC-2 and HDAC-8. Chrysin treated cells have shown increase in the levels of H3acK14, H4acK12, H4acK16 and decrease in H3me2K9 methylation. The p21 induction by chrysin treatment was found to be independent of p53 status. The chromatin remodelling at p21WAF1 promoter induces p21 activity, increased STAT-1 expression and epigenetic modifications that are responsible for ultimate cell cycle arrest and apoptosis.Conclusion
Chrysin shows in vitro anti-cancer activity that is correlated with induction of histone hyperacetylation and possible recruitment of STAT-1, 3, 5 proteins at STAT (?692 to ?684) region of p21 promoter. Our results also support an unexpected action of chrysin on the chromatin organization of p21 WAF1 promoter through histone methylation and hyper-acetylation. It proposes previously unknown sequence specific chromatin modulations in the STAT responsive elements for regulating cell cycle progression negatively via the induction of the CDK inhibitor p21 WAF1 . 相似文献20.
Rahul Bhagat Shilpa Chadaga C. S. Premalata G. Ramesh C. Ramesh V. R. Pallavi Lakshmi Krishnamoorthy 《Cellular oncology (Dordrecht)》2012,35(6):473-479