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1.
Colorectal cancer is one of the most common neoplastic diseases and a leading cause of cancer-related deaths. Overexpression of epidermal growth factor receptor (EGFR) is commonly associated with this cancer. The aim of our study was to determine the frequency of epidermal growth factor receptor gene amplification and gain in a large number of colorectal carcinomas, arranged in a tissue microarray, in order to assess their role in colorectal cancer development. A tissue microarray of 498 patients with colorectal tumors was constructed, and 239 samples for EGFR copy number changes were successfully analyzed by fluorescence in situ hybridization. No amplification of EGFR was detected in our cohort of patients with colorectal tumors, and the EGFR gene was upregulated in only 2 tumors (0.84%). Therefore, the development of colon cancer in patients cannot be explained by copy number changes of the EGFR gene. 相似文献
2.
Kenji Kitahara Wataru Yasui Hiroki Kuniyasu Hiroshi Yokozaki Yoshihiko Akama Seiji Yunotani Takeharu Hisatsugu Eiichi Tahara 《International journal of cancer. Journal international du cancer》1995,62(1):25-28
The genetic changes of cyclin A, Dl, E and CDK2 were examined in human colorectal carcinomas by Southern-blot analysis. Gene amplification of cyclin E was detected in 5 of 53 (9.4%) primary colorectal carcinoma tissues. Interestingly, in 3 of 5 tumors showing cyclin E gene amplification, the CDK2 gene was amplified simultaneously with rearrangements. No obvious correlation was detected between gene amplification and clinico-pathological features of colorectal carcinomas. Out of 7 colon carcinoma cell lines, 2 showed gene amplification of cyclin E without gene amplification of CDK2. No amplification of cyclin A or Dl gene was found in any of the colorectal carcinoma tissues or colon carcinoma cell lines. Our results suggest that the concurrent amplification of cyclin E and CDK2 genes may play a role in colorectal carcinogenesis. © 1995 Wiley-Liss Inc. 相似文献
3.
Amplification and overexpression of cyclin D1 (CCND1) have been reported as independent prognostic indicators of several tumors. To investigate the association between CCND1 amplification and overexpression in oral squamous cell carcinomas (OSCCs), and to determine which is more reliable as a prognostic indicator, fluorescence in situ hybridization (FISH) on fine-needle aspiration (FNA) biopsies and immunohistochemistry were performed on 41 primary OSCCs (26 males, 15 females; mean age; 58.4 years, range 21-89 years). Thirteen patients were stage I, 13 were stage II, nine were stage III, and six were stage IV. CCND1 amplification and overexpression was detected in 13 (31.7%) and 27 (65.9%) of 41 cases. CCND1 was overexpressed in all cases showing CCND1 amplification. On the other hand, CCND1 overexpression was also detected in 14 of 28 cases (50.0%) lacked such amplification. Statistical analysis showed that the correlation between CCND1 overexpression and decreased survival just failed to reach statistical significance, and CCND1 amplification and nodal status were independent prognostic indicators. In conclusion, it will be necessary to investigate the other pathways that regulate CCND1 expression besides CCND1 amplification. From the present study, CCND1 amplification is a more reliable prognostic indicator than CCND1 overexpression in OSCCs. 相似文献
4.
J. Ad��laide G. Monges C. D��rd��rian J. F. Seitz D. Birnbaum 《British journal of cancer》1995,71(1):64-68
The human CCND1/PRAD1 gene, located in the 11q13 chromosomal region, encodes a cyclin D protein with potential oncogenic capacity and is involved in several human malignancies. The amplification and expression status of CCND1 was investigated in a series of oesophageal tumours. CCND1 is amplified in 54% and overexpressed in 63% of the tumours of the squamous cell type. 相似文献
5.
Amplification of the cyclin D1 gene has been identified in 17-55% of head and neck squamous cell carcinoma. In some tumors, this alteration has been associated with decreased survival and increased recurrence rates. In precancerous lesions of the mouth, the frequency of cyclin D1 gene amplification is not known. In addition, it is unknown whether amplification of the gene translates to overexpressed cyclin D1 protein in these lesions. We examined 59 formalin-fixed, paraffin embedded tissue biopsies of oral epithelial dysplasias (OED) and 25 oral squamous cell carcinoma (SCC) from the floor of the mouth for cyclin D1 gene and protein levels. Genomic DNA was extracted from laser microdissected lesional tissue and a duplex, quantitative PCR assay was used to determine the amplification of the cyclin D1 gene relative to interferon-gamma. Cyclin D1 protein expression was determined using immunohistochemistry and counting positive nuclei by computer image analysis. We found cyclin D1 gene amplification in 41% of mild, 45% of moderate and 24% of severe OEDs. Cyclin D1 was amplified in 36% of SCC. Overexpression of cyclin D1 protein was identified in 29% of mild, 47% of moderate, 29% of severe OED's, and in 32% of SCC. Overexpression of cyclin D1 protein was identified in similar proportions of all grades of dysplasia and SCC. There were statistically significant correlations identified between gene and protein levels in all categories of disease. We concluded that amplification of the cyclin D1 gene is frequent in OED and that duplex, quantitative polymerase chain reaction is a reliable method to detect this change in routinely processed biopsies. The strong correlation between cyclin D1 gene amplification and protein levels suggests that this method may be suitable to assess cyclin D1 gene status in tissues not suitable for protein analysis. 相似文献
6.
Overexpression of cyclin D1 mRNA in colorectal carcinomas and relationship to clinicopathological features: Anin situ hybridization analysis 总被引:3,自引:0,他引:3
Increased expression of a key cell cycle regulator, cyclin D1, may have relevance to carcinogenesis and clinicopathological characteristics of some cancers. This study represents the first application of in situ hybridization, ISH, to detect cyclin D1 mRNA in tissue sections from colorectal carcinomas. This approach was selected because of its unique potential to clarify whether increased expression of cyclin D1 mRNA correlates with clinical and pathological parameters. The ISH ofa non-radioactive oligonucleotide probe (Biogenex) was immunocytochemically detected in paraffin embedded sections from biopsy or resection specimens. Tumors ranged from well to poorly differentiated, and from stages A, B, C, and D. Ten year survival data were available on the majority of patients. Intensity of tumor and background (smooth muscle) signals were independently scored from 0 to 3. Overexpressed cyclin D1 mRNA was seen in 86% of cases compared to background. This frequency is similar to that reported for pancreatic carcinoma. The average signal intensity score in tumor foci was 1.9 with a background score of 0.05 (p<001). All cases showed specific staining judged by the cytoplasmic localization and a tumor signal:background ratio >1. Expression did not differentiate cancers based on grade, stage or survival (p>1), but did differentiate carcinoma and severe dysplasia from mild dysplasia. We conclude that ISH of cyclin D1 mRNA is an effective and relatively specific means of detecting activity of this gene in colonic neoplasms. The high frequency of overexpression implies that gene activity by itself is not likely to predict a tumor s biological or clinical behavior. On the other hand, these data suggest that increased cyclin D1 gene activity may be an early event in colorectal carcinogenesis. They also are consistent with findings showing cyclin D1 is inducible by a variety of oncogene products. 相似文献
7.
8.
R. Pirker J. Wallner A. Gsur M. G?tzl S. Z?chbauer W. Scheithauer D. Depisch 《British journal of cancer》1993,68(4):691-694
The expression of the MDR1 gene, a multidrug resistance gene, was prospectively determined in 113 primary colorectal carcinoma specimens and correlated with clinical data including survival durations of the patients. MDR1 RNA was detected in 65% of the carcinomas. No expression of the MDR2 gene was seen, MDR1 gene expression was independent of age and sex of the patients, size and histologic grading of the tumour, lymph node involvement and distant metastasis. Kaplan-Meier analysis revealed that the durations of both relapse-free survival and overall survival were not different between patients with MDR1 RNA positive tumours and those with MDR1 RNA negative tumours. 相似文献
9.
Overexpression and amplification of cyclin D1 were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues. Overexpression of cyclin D1 was detected in 60% (263/440) and amplification of cyclin D1 was noted in 27% (119/440) of the primary breast carcinomas. Molecular analysis demonstrated that cyclin D1 was amplified in 30% (7/23) of the comedo DCIS, 22% (9/41) of the comedo DCIS and 32% (13/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 27% (9/33) of the invasive lobular carcinomas, 19% (4/21) of the colloid carcinomas and 13% (2/15) of the medullary carcinomas. Cyclin D1 was amplified in 11% (2/19) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. Our observation showed that cyclin D1 was strongly positive in 61% (14/23) of the comedo subtype, 61% (11/18) of the non-comedo subtype, 59% (24/41) of the comedo DCIS and 63% (26/41) of the adjacent invasive ductal carcinomas, 53% (10/19) of the non-comedo DCIS and 58% (11/19) of the adjacent invasive lesions, 58% (157/270) of the invasive ductal carcinomas, 73% (24/33) of the invasive lobular carcinomas, 52% (11/21) of the colloid carcinomas and 27% (4/15) of the medullary carcinomas. A significant association was observed between in situ components and adjacent invasive lesions for cyclin D1 expression (p<0.05) and amplification (p<0.05). A significant relationship was noted between amplification of cyclin D1 and lymph node metastases (p<0.05) but not with histological grade (p>0.05), estrogen receptor status (p>0.05) and proliferation index (Ki-67 and PCNA) (p>0.05). However, overexpression of cyclin D1 was statistically associated with well differentiated tumors (p<0.05) and estrogen receptor positivity (p<0.05). No relationship was seen with nodal status (p>0.05) and proliferation index (Ki-67 and PCNA) (p>0.05). These observations suggest that tumors positive for cyclin D1 protein may have features of good prognosis but amplification of cyclin D1 gene could be an indicator of tumors with poor prognostic features. Although majority of the Malaysian patients belong to younger age group (<50 years old), amplification and expression of cyclin D1 was not statistically associated with patient age (p>0.05). These observations indicate that amplification and up-regulation of cyclin D1 may be independent of patient age. Moreover, overexpression and amplification of cyclin D1 in preinvasive, preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that the gene may play an important role in early and late stages of breast carcinogenesis. 相似文献
10.
Jirström K Stendahl M Rydén L Kronblad A Bendahl PO Stål O Landberg G 《Cancer research》2005,65(17):8009-8016
Cyclins D1 and A2 are cell cycle regulators that also have the ability to interact with the estrogen receptor (ER) and consequently interfere with antiestrogen treatment in breast cancer. Experimental data support this concept, but the clinical relevance needs to be further established. In this study, we evaluated cyclin D1 and A2 protein expression by immunohistochemistry and cyclin D1 gene (CCND1) amplification by fluorescence in situ hybridization in 500 primary breast cancers arranged in tissue microarrays. Patients had been randomized to 2 years of adjuvant tamoxifen or no treatment with a median follow-up of 14 years, allowing for subgroup analysis of treatment response defined by cyclin status. We found that both cyclin D1 and A2 protein overexpression was associated with an impaired tamoxifen response, although not significant in multivariate interaction analyses, whereas tamoxifen-treated patients with CCND1-amplified tumors had a substantially increased risk for disease recurrence after tamoxifen treatment in univariate analyses [relative risk (RR), 2.22; 95% confidence interval (95% CI), 0.94-5.26; P = 0.06] in contrast to non-amplified tumors (RR, 0.39; 95% CI, 0.23-0.65; P < 0.0001). Consequently, a highly significant interaction between tamoxifen treatment and CCND1 amplification could be shown regarding both recurrence-free survival (RR, 6.38; 95% CI, 2.29-17.78; P < 0.001) and overall survival (RR, 5.34; 95% CI, 1.84-15.51; P = 0.002), suggesting an agonistic effect of tamoxifen in ER-positive tumors. In node-positive patients, the disparate outcome according to gene amplification status was even more accentuated. In summary, our data implicate that despite a significant correlation to cyclin D1 protein expression, amplification status of the CCND1 gene seems a strong independent predictor of tamoxifen response, and possibly agonism, in premenopausal breast cancer. 相似文献
11.
目的 探讨口腔鳞状细胞组织中Cyclin D1的表达与临床和病理学特征之间的关系。方法 应用免疫组化Envision二步法检测43例口腔鳞癌组织中Cyclin D1的表达情况,并将其阳性表达率与口腔鳞癌的患者性别、临床分期、病理分化程度、淋巴结转移情况以及预后做统计学分析。结果 Cyclin D1在口腔鳞癌中的阳性表达率增加,其阳性表达率与颈淋巴结转移和预后相关,但与患者性别、病理分化程度以及临床分期之间无相关性。结论 Cyclin D1异常表达在口腔鳞癌的发生、发展中发挥了重要作用,可作为判断口腔鳞癌颈淋巴结转移和预后的一个重要指标。 相似文献
12.
Antisense cyclin D1 induces apoptosis and tumor shrinkage in human squamous carcinomas. 总被引:8,自引:0,他引:8
E R Sauter M Nesbit S Litwin A J Klein-Szanto S Cheffetz M Herlyn 《Cancer research》1999,59(19):4876-4881
Cyclin D1 plays an essential regulatory role in the G1 phase of the cell cycle. The cyclin D1 gene is amplified in 20-50% of squamous cell carcinomas (SCCs), and the protein is overexpressed in up to 80% of SCCs. Our hypothesis was that gene transduction of antisense (AS) cyclin D1 in human SCCs in vivo would result in tumor reduction. A cyclin D1 cDNA was inserted into an E1/E3-deficient serotype 5 adenovirus (AS cyclin D1) in an AS orientation using homologous recombination. AS cyclin D1 transduction suppressed cyclin D1 protein expression in both cultured cells and tumors. AS cyclin D1 significantly inhibited cell proliferation by both [3H]thymidine incorporation in six SCC cell lines (P = 0.01-0.001) and the conversion of tetrazolium salt to formazan in four SCC cell lines (P = 0.01-0.004). Apoptosis detected in >25% of cells in each cell line 48 h after AS cyclin D1 transduction paralleled the reduction in cyclin D1 protein. Preformed SCCs transduced with AS cyclin D1 were significantly inhibited (P = 0.002-0.005), and apoptosis was prominent in the AS cyclin D1-treated tumors, but not in tumors treated with the control vector. These data extend prior in vitro and ex vivo results and indicate that AS cyclin D1 suppresses SCC growth both in vitro and in vivo through suppression of cyclin D1 protein expression, leading to cellular apoptosis. Our findings suggest that cyclin D1 may have a role in cell survival and that cyclin D1 AS therapy may be useful as an adjunct to standard treatment for SCC. 相似文献
13.
Polymorphisms in cyclin D1 gene and hepatocellular carcinoma 总被引:10,自引:0,他引:10
The cyclin D1 gene, CCND1, located within chromosome 11q13, plays an important role in the regulation of cell-cycle progression and has oncogenic properties. Cyclin D1 frequently is overexpressed in a variety of cancers, including hepatocellular carcinoma (HCC), as a result of gene amplification. In a previous study, we showed threefold to 20-fold amplification of CCND1 in four of 30 (13%) HCC tissues from Taiwan but not in any control liver tissues or in two HCC cell lines. A common A870G polymorphism located within the splice donor region of exon 4 of CCND1 has been reported to enhance alternate splicing. Two forms of mRNA are present in subjects with the heterozygous genotype. The relationship between the variant allele and susceptibility to HCC and clinical-pathologic outcome was investigated in 97 Taiwanese HCC patients and 35 control subjects. In this small sample, CCND1 genotype frequencies were similar in cases and controls and were not associated with susceptibility to the development of HCC. All nine patients homozygous for the G allele (GG genotype) had poorly differentiated tumors, but this association was not statistically significant, perhaps owing to the small sample. Overexpression of cyclin D1 protein, through gene amplification, correlates with poor prognosis in several cancers, but its role in HCC is the subject of controversy. Increased expression of cyclin D1 may play an important role in the development of HCC owing to the perturbation of normal control of the cell cycle. The A870G polymorphism in CCND1 may influence differentiation and prognosis in HCC patients but requires further study. 相似文献
14.
Relationship between cyclin D1 expression and poor radioresponse of murine carcinomas 总被引:5,自引:0,他引:5
Milas L Akimoto T Hunter NR Mason KA Buchmiller L Yamakawa M Muramatsu H Ang KK 《International journal of radiation oncology, biology, physics》2002,52(2):514-521
PURPOSE: We recently reported that overexpression of epidermal growth factor receptor (EGFR) positively correlated with radioresistance of murine carcinomas. Because cyclin D1 is a downstream sensor of EGFR activation, the present study investigated whether a relationship exists between the extent of cyclin D1 expression and in vivo radiocurability of murine tumors. We further investigated the influence of radiation on cyclin D1 expression and the expression of p27, an inhibitor of the cyclin D1 downstream pathway, as well as the relationship of these molecular determinants to cell proliferation and induced apoptosis in tumors exposed to radiation. METHODS AND MATERIALS: Cyclin D1 expression was assayed in nine carcinomas syngeneic to C3Hf/Kam mice using Western blot analysis. These tumors greatly differed in their radioresponse as assessed by TCD(50). The expression of cyclin D1 and p27 proteins was determined by Western blotting. Cell proliferative activity in tumors was determined by proliferating cell nuclear antigen (PCNA) immunochemistry. The effect of irradiation on the expression of cyclin D1 or p27 proteins and on PCNA positivity was determined in the radiosensitive OCa-I and in the radioresistant SCC-VII tumors. RESULTS: Cyclin D1 expression varied among tumors by 40-fold, and its magnitude positively correlated with poorer tumor radioresponse (higher TCD(50) values). The level of cyclin D1 expression paralleled that of EGFR. A 15-Gy dose reduced constitutive expression of cyclin D1 in the radiosensitive OCa-I tumors, but had no influence on expression of cyclin D1 in the radioresistant SCC-VII tumors. In contrast, 15 Gy increased the expression of p27 in radiosensitive tumors and reduced it in radioresistant tumors. Radiation induced no significant apoptosis or change in the percentage of PCNA-positive (proliferating) cells in SCC-VII tumors with high cyclin D1 levels, but it induced significant apoptosis and a decrease in the percentage of proliferating cells in OCa-I tumors with low cyclin D1 expression. CONCLUSION: Our findings show a positive correlation between cyclin D1 expression and tumor radioresistance. The expression of cyclin D1 and p27 was modified by radiation and was associated with cellular response to radiation, but this depended on the pretreatment level of cyclin D1 expression. These findings may have important clinical implications: The pretreatment assessment of cyclin D1 expression could serve as a useful predictor of radiotherapy outcome and assist in selecting an effective treatment modality. 相似文献
15.
Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas 总被引:4,自引:0,他引:4
Lewis RC Bostick RM Xie D Deng Z Wargovich MJ Fina MF Roufail WM Geisinger KR 《Cancer research》2003,63(23):8549-8553
Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis coli-beta-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G(1) to S-phase cell cycle transition, promoting cell proliferation. A recently described codon 242, exon 4, G to A single nucleotide polymorphism (A870G) produces a longer half-life cyclin D1. To investigate whether CCND1 genotype influences risk for colorectal adenoma, we genotyped CCND1 by PCR/RFLP on 161 incident sporadic adenoma cases and 213 controls ages 30-74 years in a North Carolina colonoscopy-based case-control study. At least one polymorphic A allele was found in 68% of cases and 60% of controls. Having an A allele was associated with increased risk for adenoma: the age- and sex-adjusted odds ratio (OR) was 1.5 [95% confidence interval (CI) 1.0-2.4], a finding that was stronger for those whose adenomas were multiple (OR 2.9, 95% CI 1.4-6.0), larger (>or=1 cm; OR 2.4, 95% CI 1.2-4.8), had moderate to severe dysplasia (OR 2.1, 95% CI 1.1-3.8), or were in the right side of the colon (OR 3.6, 95% CI 1.3-10.0). Joint risk factor multivariate analyses revealed stronger positive associations among those who were older (>57 years; OR 2.8, 95% CI 1.4-5.5), male (OR 2.8, 95% CI 1.3-5.7), currently smoked (OR 2.7, 95% CI 1.3-5.7), or currently drank alcohol (OR 2.2, 95% CI 1.2-4.2) if they had an A allele and stronger inverse associations among those who used nonsteroidal anti-inflammatory drugs (OR 0.4, 95% CI 0.2-0.9) or had higher calcium intakes (OR 0.4, 95% CI 0.2-0.9) if they had no A allele. These data support the hypothesis that the CCND1 A870G polymorphism may increase risk for colorectal neoplasms. 相似文献
16.
Henriksson E Baldetorp B Borg A Kjellen E Akervall J Wennerberg J Wahlberg P 《Acta oncologica (Stockholm, Sweden)》2006,45(3):300-305
To investigate the response of tumour growth to cisplatin treatment, in relation to p53 mutation and cyclin D1 dysregulation on DNA and protein level, biopsies from seven xenografted human squamous cell carcinomas from the head and neck were analysed with immunohistochemistry for p53 expression and cyclin D1 expression. Polymerase chain reaction-singlestranded conformation polymorphism was used to determine p53 mutations. Fluorescence in situ hybridization was performed to analyse cyclin D1 amplification. The mice were injected i.p. with NaCl (controls) or cisplatin. After injection the tumour volume were measured. The inhibition of tumour growth by cisplatin was defined as the area under the growth curves, and compared with the growth curves of the tumours in the control group. Xenografts with p53 mutation showed significantly higher resistance to cisplatin (p < 0.001) and also tumours with cyclin D1 amplification showed significantly higher resistance (p < 0.001). 相似文献
17.
Adenoid cystic carcinoma (ACC) of the salivary glands exhibits persistent growth, invasion and metastasis. Chromosome 11q13 amplification is a frequent event associated with tumor progression in a number of carcinomas and is associated with poor prognosis. Two genes within the 11q13 amplicon that are overexpressed as a result of 11q13 amplification are the cell cycle regulatory protein cyclin D1 (CCND1) and cortactin (CTTN), a protein involved cell motility and invasion. To determine the expression and gene status of cyclin D1 and cortactin in ACC, we evaluated 39 ACC cases by immunohistochemistry (IHC) for cyclin D1 and cortactin expression. Amplification of CCND1 and CTTN was determined by fluorescent in situ hybridization (FISH). Cyclin D1 overexpression was present in 90% (35/39) and cortactin expression in 62% (24/39) of evaluated cases, although CCND1 and CTTN levels were elevated in only two cases (5%) as determined by FISH. Our results indicate that chromosome 11q13 amplification is uncommon in ACC, but that cyclin D1 and cortactin are frequently overexpressed and may therefore contribute to the growth and invasive potential of ACC. 相似文献
18.
Javier del Rey Esther Prat Immaculada Ponsa Josep Lloreta Antoni Gelabert Ferran Algaba Jordi Camps Rosa Miró 《BMC cancer》2010,10(1):280
Background
Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. 相似文献19.
Cyclin D1 is a cell cycle regulator which is overexpressed in a variety of human cancers. We examined overexpression of cyclin D1 in several stages of rat colorectal carcinogenesis induced by azoxymethane (AOM) treatment. The level of cyclin D1 in 13 aberrant crypt foci (ACF) (atypical hyperplasias), 22 colorectal tumors (14 non-invasive adenocarcinomas and eight invasive adenocarcinomas) was assessed by immunostaining using a polyclonal antibody. Cell proliferation of these samples was investigated by measurement of 5-bromo-2′-deoxyuridine-labeling index. Indices of cyclin D1-positive cells in adenocarcinomas and atypical hyperplasias were significantly higher than that in normal crypts (P<0.05). Moreover, cyclin D1-positive rates in the two types of adenocarcinomas were significantly higher than that in atypical hyperplasias (P<0.05). Staining of nuclear cyclin D1 was very strong in almost all adenocarcinomas and four ACF. Comparisons of BrdU-positive indices in colorectal lesions showed similar results to the cyclin D1-positive indices. These results suggested that overexpession of cyclin D1 occurs early in the multistep carcinogenesis, and plays an important role in rat colorectal carcinogenesis. 相似文献
20.
Frank Courjal Genevive Louason Paul Speiser Dionisios Katsaros Robert Zeillinger Charles Theillet 《International journal of cancer. Journal international du cancer》1996,69(4):247-253
Evidence of the involvement of cyclin genes in genetic alterations in human cancer is growing. In the present study, we investigated the amplification, in human breast and ovarian cancer, of 5 cyclin genes; cyclin A, cyclin D1, cyclin D2, cyclin D3 and cyclin E. For this purpose, a series of 1,171 breast and 237 ovarian tumors tested for DNA amplification by Southern blotting and a subset of 132 breast and 22 ovarian cancers were analyzed for RNA expression levels by slot-blot and Northern blotting. In breast tumors, only cyclin D1 was found to be activated in a sizeable fraction of the tumors (amplification 12.6%, overexpression 19%). Cyclin A, D2, D3, and E genes never, or only on rare occasions, showed increased DNA copy numbers and were never found overexpressed at the RNA level. Amplification of cyclin D1 correlated with ER+ breast cancer and the presence of lymph-node metastasis. Interestingly, we were also able to determine an association with invasive lobular carcinoma. Our data suggest that cyclin D1 activation determines the evolution of a particular subset of estrogen-responsive tumors. Data obtained in ovarian tumors contrasted with observations in breast cancer. Cyclin D1 DNA amplification was much less frequent in ovarian than in breast tumors (3.3% vs. 12.6%), whereas cyclin E amplification and overexpression were observed in a significant number of cases (12.5% and 18.0% respectively). Cyclin A, cyclin D2 and D3 rarely showed anomalies at the DNA level and were never overexpressed. No clear correlation could be observed between amplification of the cyclin E gene and tumor type, stage or grade in ovarian cancer. Data presented here suggest distinct pathways of cyclin activation in human breast and ovarian cancer. © 1996 Wiley-Liss, Inc. 相似文献