共查询到20条相似文献,搜索用时 31 毫秒
1.
Hiroo Nakajima Naruhiko Mizuta Koichi Sakaguchi Ikuya Fujiwara Atsushi Yoshimori Satoshi Takahashi Ryoko Takasawa Sei-ichi Tanuma 《Breast cancer (Tokyo, Japan)》2008,15(1):65-72
An antagonistic peptide called HRAP that binds to the human HER2 molecule was designed by our computational method. In silico docking study demonstrated the specific interaction of HRAP with the dimerization domain in the HER2 molecule. Interestingly, HRAP inhibited proliferation of HER2-overexpressed human breast cancer cell lines. However, it had little cellular cytotoxicity (apoptosis inducibility). The cell proliferation inhibition was associated with the suppression of phosphorylation of PTEN and Akt. Thus, HRAP is the first HER2-binding small peptide antagonist rationally designed by a computer-aided SBDD method and is useful for the development of peptide mimetics to generate novel anti-breast cancer drugs. 相似文献
2.
Woll MM Hueman MT Ryan GB Ioannides CG Henderson CG Sesterhan IA Shrivasta S McLeod DG Moul JW Peoples GE 《International journal of oncology》2004,25(6):1769-1780
The HER2/neu protein is over-expressed in multiple epithelial tumors and the source of immunogenic peptides currently under investigation in vaccine trials in ovarian and breast cancers. We sought to define the correlation between HER2/neu expression and risk for prostate cancer recurrence and then determine the potential efficacy of anti-HER2/neu vaccination in prostate cancer patients at risk for recurrence. The risk for prostate-specific antigen (PSA) recurrence in 95 patients undergoing prostatectomy at the Walter Reed Army Medical Center (WRAMC) was calculated and correlated to HER2/neu expression, as determined by immunohistochemical staining. Peripheral blood lymphocytes (PBL) were then isolated from six consecutive human leukocyte antigen (HLA) A2+ patients with HER2/neu+ prostate tumors. These PBL were grown in parallel cultures and stimulated either with no peptide, HER2/neu E75 peptide, or control peptide. The cultures were compared for stimulated proliferation, induced peptide-specific cytotoxicity and tumor-specific cytotoxicity. When assessed by risk group, 69% of the high risk patients' tumors over-expressed HER2/neu compared to 47% of the intermediate risk group (p<0.05). Evaluation of the in vitro immune response of PBL isolated from six consecutive prostate cancer patients revealed a statistically significant increase in E75-stimulated lymphocytic proliferation. E75-stimulated lymphocytes demonstrated an E75-specific cytolytic response in 6/6 prostate cancer patients that increased with successive stimulations. Moreover, these E75-specific lymphocytes also demonstrated tumor-specific lysis against HER2/neu-expressing prostate cancer cell lines. The majority of prostate cancer patients at high risk for recurrence have HER2/neu expressing tumors. Hence, HER2/neu is a viable target for immunotherapeutics such as preventative immunization strategies with HER2/neu peptide vaccines. 相似文献
3.
Zhenghu Li Zhi-Qiang Ling Weiwei Guo Xiao-Xiao Lu Yi Pan Zhenzhen Wang Yan Chen 《Oncotarget》2015,6(14):12357-12368
PAQR3 is a newly discovered tumor suppressor and its functional role in breast cancer has not been well characterized. We report here that PAQR3 is associated with the progression and survival of human patients with breast cancer, as well as cell proliferation and migration of human breast cancer cells. PAQR3 mRNA level was robustly downregulated in human breast cancer samples compared with their corresponding para-cancerous histological normal tissues (n = 82, P < 0.0001). The mRNA level of PAQR3 was negatively correlated with HER2 expression (P < 0.0001) and disease-free survival of the patients (P < 0.0001). PAQR3 overexpression inhibited cell proliferation, colony formation and migration of breast cancer cells including MCF7, SKBR3, MDA-MD-231, MDA-MD-468 and MDA-MD-453 cells. Knockdown of PAQR3 in MDA-MD-231 cells elevated cell proliferation and migration. Inhibition of HER2 by trastuzumab increased PAQR3 expression in SKBR3 cells. In conclusion, PAQR3 expression is frequently downregulated in human breast cancers inversely correlated with HER2 expression. PAQR3 is able to modulate the proliferation and migration of breast cancer cells. Our data indicate that PAQR3 functions as a tumor suppressor in the development of human breast cancers. 相似文献
4.
Ramón Colomer Ruth Lupu Adriana Papadimitropoulou Luciano Vellón Alejandro Vázquez-Martín Joan Brunet Alberto Fernández-Gutiérrez Antonio Segura-Carretero Javier A. Menéndez 《Clinical & translational oncology》2008,10(1):30-34
We are accumulating evidence to suggest that 17th century Renaissance foodways-largely based on the old “Mediterranean dietary traditions”-may provide new nutraceutical management
strategies against HER2-positive breast cancer disease in the 21st century. Epidemiological and experimental studies begin
to support the notion that “The Sacred Law of Salads” (i.e., “raw vegetables…plenty of generous (olive) oil”)-originally proposed
in 1614 by Giacomo Castelvetro in its book The Fruit, Herbs & Vegetables of Italy-might be considered the first (unintended) example of customised diets for breast cancer prevention based on individual genetic
make-up (i.e., nutraceuticals against human breast carcinomas bearing HER2 oncogene amplification/overexpression). First,
the so-called salad vegetables dietary pattern (i.e., a high consumption of raw vegetables and olive oil) appears to exert
a protective effect mostly confined to the HER2-positive breast cancer subtype, with no significant influence on the occurrence
of HER2-negative breast cancers. Second, all the main olive oil constituents (i.e., the ω-9 monounsaturated fatty acid oleic
acid and polyphenolic compounds such as the secoiridoid oleuropein or the lignan 1-[+]-acetoxypinoresinol] dramatically reduce
HER2 expression and specifically induce apoptotic cell death in cultured HER2-positive breast cancer cells, with marginal
effects against HER2-negative cells. Third, an olive oil-rich diet negatively influences experimental mammary tumorigenesis
in rats likewise decreasing HER2 expression levels. If early 1600s Castelvetro’s salads can be used as dietary protocols capable
to protecting women against biologically aggressive HER2-positive breast cancer subtypes is an intriguing prospect that warrants
to be evaluated in human pilot studies in the future. Here, at least, we would like to recognise Giacomo Castelvetro as the
father of modern nutritional genomics in oncology. 相似文献
5.
Ikuta Y Okugawa T Furugen R Nagata Y Takahashi Y Wang L Ikeda H Watanabe M Imai S Shiku H 《International journal of cancer. Journal international du cancer》2000,87(4):553-558
We have identified an H-2K(d)-binding peptide, HER2p780 (PYVSRLLGI), derived from murine HER2/neu (HER2), that can induce HER2-specific murine cytotoxic T lymphocytes (CTL). Weekly vaccination of BALB/c mice by syngeneic dendritic cells pulsed with HER2p780 peptide, entirely common to murine and human HER2, suppressed growth of pretransplanted HER2-expressing syngeneic tumors. A HER2-expressing human cancer cell line SKOV3 transfected with murine H-2K(d) cDNA could also be lysed by HER2p780-specific murine CTLs, indicating that human HER2-expressing cancer cells can process and present the cognate peptide in the context of H-2K(d). Since H-2K(d) and HLA-A2402 molecules have similar anchor motifs, the possibility of inducing HER2-specific CTL activity with HER2p780 in HLA-A2402 individuals was examined. CD8(+) CTL clones specific for HER2-expressing cancer cell lines were established from peripheral blood lymphocytes with HLA-A2402 by repeatedly sensitizing with peptide-pulsed autologous dendritic cells as well as peripheral blood mononuclear cells. Detailed analysis of their specificity revealed that the cytotoxicity of CTL clones is specific for the cognate peptide with HLA-A2402 restriction. The results suggest that HER2p780 is a unique peptide that may function as a tumor rejection antigen peptide in HLA-A2402 individuals, as it was directly proven here to function in a murine tumor system. 相似文献
6.
Huang C Park CC Hilsenbeck SG Ward R Rimawi MF Wang YC Shou J Bissell MJ Osborne CK Schiff R 《Breast cancer research : BCR》2011,13(4):R84
Introduction
The overexpression of human epidermal growth factor receptor (HER)-2 in 20% of human breast cancers and its association with aggressive growth has led to widespread use of HER2-targeted therapies, such as trastuzumab (T) and lapatinib (L). Despite the success of these drugs, their efficacy is limited in patients whose tumors demonstrate de novo or acquired resistance to treatment. The β1 integrin resides on the membrane of the breast cancer cell, activating several elements of breast tumor progression including proliferation and survival. 相似文献7.
HER2/neu过表达通过PI3K/Akt通路对乳腺癌细胞MCF7中p53基因表达及细胞生长和放疗敏感性的影响 总被引:11,自引:2,他引:9
目的 研究HER2/neu基因过表达通过磷脂酰肌醇-3-激酶(PI3K)通路对乳腺癌细胞MCF7野生型p53基因表达、细胞增殖及对γ射线照射敏感性的影响。方法 以脂质体介导的HER2/neu基因转染MCF7细胞,用G418筛选阳性克隆。通过Western blot鉴定HER2/neu蛋白的表达,并检测p53、信号转导分子Akt和p-Akt蛋白含量的变化及PI3K通路抑制剂LY294002对上述蛋白表达水平的影响。以MTT法检测细胞增殖以及细胞对γ射线照射的敏感性。结果 共获得18个稳定转染HER2/neu基因的阳性克隆,其中1个克隆有HER2/neu基因过表达。过表达HER2/neu的MCF7细胞p-Akt蛋白含量升高,p53蛋白含量低于对照组细胞,LY294002能够抑制p-Akt蛋白和p53蛋白的变化。同时,过表达HER2/neu基因的MCF7细胞生长速度高于对照组细胞,对γ射线照射治疗的敏感性降低,而LY294002能够抑制细胞生长并增强放射治疗的敏感性。结论 MCF7细胞中HER2/neu基因的过表达,能够通过激活PI3K通路导致野生型p53蛋白含量减少、细胞增殖加快及放疗的敏感性降低,这可能是某些p53蛋白为野生型的肿瘤患者对治疗产生抗性的原因。 相似文献
8.
Bayraktar UD Kim TK Drews-Elger K Benjamin C El-Ashry D Wieder E Komanduri KV 《Breast cancer research and treatment》2011,129(2):623-628
The activation of human epidermal growth factor receptor-2 (HER2) results in the activation of the mitogen-activated protein
kinase (MAPK) cascade that may lead to the resistance to anti-estrogen therapy in estrogen receptor (ERα) expressing breast
cancer by means of phosphorylation of ERα in the N-terminal region by phosphorylated extracellular signal-regulated kinase
1/2 (pERK1/2) and by means of decreasing ERα expression. Immunohistochemistry is the most widely used technique for the detection
of ERα and HER2 in breast cancer specimens, however, is inadequate in its ability to assess the relationship between ERα,
HER2, and MAPK cascade at the single cell level. To clear this major hurdle, we devised a novel flow cytometric method to
quantify the expression of ERα, HER2, and the activation of MAPK cascade simultaneously in single cells. The method was validated
by concurrent Western blotting in established cell lines: MDA-231 (ERα and HER2-negative), MCF-7 (ERα-positive, HER2-negative),
MCF-7 cells overexpressing ERα after long-term incubation in estrogen-free medium, and HER2 transfected MCF7 cells. Using
the flow cytometry method, we confirmed the previous finding that ERα expression is down-regulated upon epidermal growth factor
mediated ERK1/2 phosphorylation in EGFR/MCF-7 cells. To our knowledge, this is the first such assay to incorporate simultaneous
single cell measurement for all of these pathways, which may prove useful to determine the intratumoral heterogeneity in breast
tumors or the receptor status in circulating tumor cells. 相似文献
9.
10.
Farah B. Rahmatpanah Zhenyu Jia Xin Chen Jessica E. Char Bozhao Men Anna-Clara Franke Frank E. Jones Michael McClelland Dan Mercola 《Oncotarget》2015,6(2):1286-1301
HER2-positive breast cancer accounts for 25% of all cases and has a poor prognosis. Although progress has been made in understanding signal transduction, little is known of how HER2 achieves gene regulation. We performed whole genome expression analysis on a HER2+ and HER2− breast cancer cell lines and compared these results to expression in 812 primary tumors stratified by their HER2 expression level. Chip-on-chip with anti-RNA polymerase II was compared among breast cancer cell lines to identify genes that are potentially activated by HER2. The expression levels of these HER2-dependent POL II binding genes were determined for the 812 HER2+/− breast cancer tissues. Genes differentially expressed between HER2+/− cell lines were generally regulated in the same direction as in breast cancer tissues. We identified genes that had POLII binding in HER2+ cell lines, but without significant gene expression. Of 737 such genes “poised” for expression in cell lines, 113 genes were significantly differentially expressed in breast tumors in a HER2-dependent manner. Pathway analysis of these 113 genes revealed that a large group of genes were associated with stem cell and progenitor cell control as indicated by networks centered on NANOG, SOX2, OCT3/4. HER2 directs POL II binding to a large number of genes in breast cancer cells. A “poised” class of genes in HER2+ cell lines with POLII binding and low RNA expression but is differentially expressed in primary tumors, strongly suggests a role of the microenvironment and further suggests a role for stem cells proliferation in HER2-regulated breast cancer tissue. 相似文献
11.
Roomi MW Ivanov V Kalinovsky T Niedzwiecki A Rath M 《Medical oncology (Northwood, London, England)》2007,24(2):183-188
Current treatment of testicular cancer is associated with secondary malignancy, infertility, and cytotoxicity. Based on reported
antimetastatic potential, we investigated the effect of a nutrient mixture (NM) containing lysine, proline, arginine, ascorbic
acid, and green tea extract on human testis cancer cell line NT 2/DT by measuring cell proliferation/cytotoxicity, modulation
of MMP-2 and MMP-9 secretion, and cancer cell invasive potential. Human testis cancer cells NT 2/DT (ATCC) were grown in DME
medium. At near confluence, the cells were treated with NM dissolved in media and tested at 0,10, 50, and 100 Μg/mL in triplicate
at each dose. Cells were also treated with PMA 200 ng/mL to study enhanced secretion of MMP-9. Cell proliferation/cytotoxicity
was evaluated by MTT assay, MMP activity by gelatinase zymography, and invasion through Matrigel. The nutrient mixture showed
no significant effect on testis cancer cell growth. Zymography demonstrated secretion of MMP-2 by untreated human testis cancer
cells and MMP-9 with PMA induction. NM inhibited secretion of both MMPs in a dose-dependent fashion with virtual total inhibition
of MMP-9 at 100 Μg/mL. Invasion of human testis cancer cells through Matrigel was reduced by 84% at 50 Μg/mL and at 100 Μg/mL
(p = 0.004). NM significantly inhibited MMP secretion and matrix invasion in testicular cancer cells without toxic effect, indicating
potential as an anticancer agent. 相似文献
12.
Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cells 总被引:10,自引:0,他引:10
Faltus T Yuan J Zimmer B Krämer A Loibl S Kaufmann M Strebhardt K 《Neoplasia (New York, N.Y.)》2004,6(6):786-795
In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of gene expression referred to as RNA interference (RNAi). We exploited RNAi to define the role of HER2/neu in the neoplastic proliferation of human breast cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer cells with short interfering RNA (siRNA) targeted against human HER2/neu and analyzed the specific inhibition of HER2/neu expression by Northern and Western blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific decrease in HER2/neu mRNA and protein levels. Moreover, transfection with HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines SK-BR-3 and BT-474, consistent with a powerful RNA silencing effect. siRNA treatment resulted in an antiproliferative and apoptotic response in cells overexpressing HER2/neu, but had no influence in cells with almost no expression of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu function is essential for the proliferation of HER2/neu-overexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as antiproliferative agents that display activity against neoplastic cells at very low doses. 相似文献
13.
Down-regulation of HER2/neu expression induces apoptosis in human cancer cells that overexpress HER2/neu 总被引:10,自引:0,他引:10
The HER2/neu oncogene is overexpressed in a significant fraction of human tumors; such overexpression is thought to play a role in the aberrant proliferation of cancer cells. The effects of HER2/neu-specific phosphorothioate antisense oligodeoxyribonucleotides on HER2/neu expression, tumor cell proliferation, and activation of apoptotic cell death pathways have been examined. Antisense treatment down-regulates HER2/neu expression in a dose-dependent and sequence-specific manner. HER2/neu antisense treatment specifically inhibits the growth of tumor lines that overexpress HER2/neu, but it has little effect on the growth of tumor cells that express low levels of HER2/neu. Down-regulation of HER2/neu expression is not only cytostatic, but it also results in the activation of apoptotic cell death pathways in cells that overexpress HER2/neu. These results suggest that, in addition to stimulating tumor cell proliferation, HER2/neu overexpression in cancer cells acts as an antiapoptotic cell survival factor. 相似文献
14.
Baek JM Jin Q Ensor J Boulbes DR Esteva FJ 《Breast cancer research and treatment》2011,130(3):1029-1036
CD44 is an adhesion molecule involved in tumor cell invasion and metastasis. The function of CD44 in breast cancer is not
understood completely, or is its role as a predictive or prognostic factor. In this study, we tested for the hypothesis that
the concentration of soluble CD44 (sCD44) in serum is correlated with clinicopathological factors, especially HER2, and survival
in patients with breast cancer. We retrospectively identified 110 patients with breast cancer who had been treated at The
University of Texas MD Anderson Cancer Center (MDACC) from September 2001 to May 2004. Sera were collected before definitive
surgery in patients with stage I or II breast cancer, before initiation of neoadjuvant chemotherapy (if indicated) for patients
with stage I–III breast cancer, and before initiation of systemic therapy in patients with stage IV breast cancer. sCD44 levels
were determined using an enzyme-linked immunosorbent assay. The median age at diagnosis was 51 years (range, 28.6–87.1 years).
sCD44 concentration was correlated with tumor stage (P = 0.0308). sCD44 serum concentration did not predict pathological response in patients treated with neoadjuvant chemotherapy.
Among patients with distant metastases, sCD44 levels were significantly higher in patients with liver involvement than in
patients with metastases at other sites. The overall survival rate did not differ between patients with high sCD44 concentration
and patients with low sCD44 concentration. However, sCD44 concentration was a significant predictor of overall survival for
patients with HER2-positive breast cancer, while no difference in overall survival rates was observed in patients with HER2-negative
breast cancer. To the best of our knowledge, this is the first study to show an association between circulating sCD44 levels
and survival in HER2-positive breast cancer patients. Our results suggest a role for sCD44 as a prognostic marker. Furthermore,
sCD44 level may offer a new clinical therapeutic target in HER2-positive breast cancer. 相似文献
15.
Britta Weigelt Alvin T. Lo Catherine C. Park Joe W. Gray Mina J. Bissell 《Breast cancer research and treatment》2010,122(1):35-43
Development of effective and durable breast cancer treatment strategies requires a mechanistic understanding of the influence
of the microenvironment on response. Previous work has shown that cellular signaling pathways and cell morphology are dramatically
influenced by three-dimensional (3D) cultures as opposed to traditional two-dimensional (2D) monolayers. Here, we compared
2D and 3D culture models to determine the impact of 3D architecture and extracellular matrix (ECM) on HER2 signaling and on
the response of HER2-amplified breast cancer cell lines to the HER2-targeting agents Trastuzumab, Pertuzumab and Lapatinib. We show that the response
of the HER2-amplified AU565, SKBR3 and HCC1569 cells to these anti-HER2 agents was highly dependent on whether the cells were cultured
in 2D monolayer or 3D laminin-rich ECM gels. Inhibition of β1 integrin, a major cell–ECM receptor subunit, significantly increased
the sensitivity of the HER2-amplified breast cancer cell lines to the humanized monoclonal antibodies Trastuzumab and Pertuzumab when grown in a 3D environment.
Finally, in the absence of inhibitors, 3D cultures had substantial impact on HER2 downstream signaling and induced a switch
between PI3K-AKT- and RAS-MAPK-pathway activation in all cell lines studied, including cells lacking HER2 amplification and overexpression. Our data provide direct evidence that breast cancer cells are able to rapidly adapt to
different environments and signaling cues by activating alternative pathways that regulate proliferation and cell survival,
events that may play a significant role in the acquisition of resistance to targeted therapies. 相似文献
16.
Breast cancer is the most common cancer among women. It is estimated that 7% of women who have breast cancer will develop
a subsequent second independent breast tumor within 10 years of the first. The status of estrogen (ER), progesterone (PR)
and human growth hormone (HER2) receptors, individually and as phenotypic combinations, impacts the clinical course of breast
cancer and may impact the course of subsequent primary tumors and patient survival. Our aims were to determine tumor marker
phenotype concordance between first and second primary breast cancers (FPBC and SPBC), describe demographic and clinical characteristics,
and examine first tumor treatments associated with phenotype concordance. A total of 76,209 cases of female invasive breast
cancer were identified in the California Cancer Registry from 1999 to 2004. Of those, 1,407 women who had not undergone a
prophylactic mastectomy, had information on the status of three tumor markers, and were diagnosed with an SPBC during the
study period were selected. SPBCs were significantly smaller, diagnosed at a higher stage and were node positive. Patients
whose FPBC was ER+/−/PR+/−/HER2− and triple negative (TN) (ER−/PR−/HER2−), often had concordant phenotypes for their SPBC. ER+/−/PR+/−/HER2+ and HER2-positive (ER−/PR−/HER2+) FPBCs, often had discordant phenotypes for their SPBC. ER+/−/PR+/−/HER2− SPBCs often lacked HER2 expression and were ER and/or PR positive. Tumor laterality and synchronicity significantly
predicted concordance as did having a FPBC whose phenotypes were ER+/−/PR+/−/HER2+, HER2-positive and TN, while first primary tumor treatment with chemotherapy predicted discordance. The relationship
between multiple primary breast cancer phenotype concordance and patient prognosis has yet to be determined. Our results indicate
that SPBC surveillance strategies include consideration of FPBC phenotype. Although our results are provocative, they may
have been influenced by current criteria used to determine tumor independence. 相似文献
17.
Although anti-HER2 (human epidermal growth factor receptor 2) therapy is currently approved for breast, gastric, and gastroesophageal cancers overexpressing the HER2 protein or amplified for the HER2 gene, HER2 aberrations (gene amplification, gene mutations, and protein overexpression) are reported in other diverse malignancies. Indeed, about 1–37% of tumors of the following types harbor HER2 aberrations: bladder, cervix, colon, endometrium, germ cell, glioblastoma, head and neck, liver, lung, ovarian, pancreas, and salivary duct. Four HER2-targeted therapies have been approved for HER2-positive breast cancer: two antibodies (trastuzumab and pertuzumab), an antibody-drug conjugate (ado-trastuzumab emtansine), and a small molecule kinase inhibitor (lapatinib). In addition, afatinib, a small molecule kinase inhibitor that causes irreversible inhibition of EGFR (epidermal growth factor receptor) and HER2, was recently approved for EGFR-mutated non-small cell lung cancer. A large number of novel HER2-targeted agents are also in clinical trials. Herein we discuss the state of the art in understanding and targeting HER2 across anatomic tumor types. 相似文献
18.
HER2 (also known as ErbB2) is a transmembrane tyrosine kinase whose surface overexpression is linked to tumorigenesis and poor prognosis in breast cancer patients. beta-catenin is a substrate of this kinase, and HER2-dependent phosphorylation of tyrosine 654 leads to dissociation of the E-cadherin-beta-catenin membrane complex and increased Wnt signaling. beta-catenin-mediated Wnt signaling promotes proliferation and invasion of breast cancer cells. In this study, we show that HER2 binds to beta-catenin and that geldanamycin (GA), a drug that destabilizes HER2 protein, causes rapid depletion of HER2, thereby disrupting its association with beta-catenin in SKBr3 human breast cancer cells. Interestingly, GA did not affect the stability of beta-catenin protein, but altered its subcellular localization, driving it out of the nucleus and increasing its association with E-cadherin. Importantly, the change in subcellular localization of beta-catenin was also associated with a significant decrease in proliferation and motility of GA-treated breast cancer cells. Moreover, GA treatment led to reduced expression of the Wnt signaling target and cell cycle-promoting gene cyclin D1, providing a potential mechanism for the reduced proliferation. In conclusion, GA treatment suppressed tumorigenicity in the human breast cancer cell line SKBr3, at least in part through destabilization of the HER2 oncoprotein and repression of the Wnt/beta-catenin signaling pathway. These findings provide evidence for the clinical importance of GA in treatment of HER2 overexpressing breast cancers. 相似文献
19.
目的 观察小鼠成纤维细胞系3T3来源的外泌小体(exosome)对小鼠乳腺癌细胞4T1增殖能力的影响,并探索其中可能的机制。方法 PureExo Exosome提取试剂盒提取3T3细胞上清液中的exosome,按照不同浓度及时间作用于4T1细胞,CCK8法检测4T1细胞的增殖能力,BrdU/PI双掺入法测定细胞DNA合成及细胞周期;免疫印迹法(Western blot)及荧光定量实时PCR(qPCR)检测人表皮生长因子受体2(epidermal growth factor receptor-2, EGFR2,也称HER2)及下游PI3K/AKT信号转导通路相关蛋白的变化。利用HER2单克隆抗体靶向药物赫赛汀(Herceptin),观察exosome是否影响4T1细胞对于Herceptin敏感度。结果 exosome处理组OD450吸光度值显著高于对照组(P<0.05),细胞增殖及细胞周期进程加快。Western blot及qPCR实验提示随着exosome浓度的增加,HER2表达逐渐升高, AKT磷酸化水平增加。而同时给予exosome可明显增加4T1细胞对Herceptin的敏感度。结论 小鼠成纤维细胞系3T3来源exosome可促进小鼠乳腺癌细胞4T1增殖及周期进程,并且可能通过HER2激活其下游PI3K/AKT信号通路发挥上述作用。 相似文献
20.
Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model 总被引:9,自引:0,他引:9
Matsui Y Inomata M Tojigamori M Sonoda K Shiraishi N Kitano S 《International journal of oncology》2005,27(3):681-685
New modalities are necessary for the treatment of patients with unresectable gastric cancer. The aim of this study was to investigate whether or not anti-HER2 antibody could suppress the growth of human gastric cancer cells with HER2 overexpression in vitro and in vivo. Four human gastric cancer cell lines, NCI-N87, MKN-45P, Kato-III, and MKN-1, were used in this study. The suppression of cell proliferation in vitro and of subcutaneous tumor growth in a nude mouse model after treatment with trastuzumab was examined. The expression of HER2 protein was investigated by Western blot analysis. The effect of trastuzumab on the survival rate of nude mice with peritoneal dissemination was examined. Trastuzumab significantly reduced proliferative activity in NCI-N87, a HER2-overexpressing human gastric cancer cell line, in vitro. In the nude mouse model with transplanted subcutaneous tumor, trastuzumab significantly suppressed the tumor growth of NCI-N87 cells, and then HER2 expression was reduced. Trastuzumab improved the survival rate of mice with peritoneal dissemination of MKN-45P cells. Trastuzumab therapy is a potential candidate for a novel treatment of HER2-overexpressing gastric cancer. 相似文献