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乳腺癌细胞中生长抑素受体与表皮生长因子受体的共定位

Colocalization of somatostatin receptors and epidermal growth factor receptors in breast cancer cells.

作者信息

Watt Heather L, Kumar Ujendra

机构信息

Fraser Laboratories For Diabetes Research, Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, H3A 1A1, Canada.

出版信息

Cancer Cell Int. 2006 Mar 6;6:5. doi: 10.1186/1475-2867-6-5.

Abstract

BACKGROUND

Somatostatin receptor (SSTR) expression is positively correlated with tumor size and inversely correlated with epidermal growth factor receptor (ErbB) levels and tumor differentiation. In the present study, we compared SSTR1-5 and ErbB1-4 mRNA and protein expression in two breast cancer cell lines: MCF-7 (ER+) and MDA-MB-231 (ERalpha-).

RESULTS

All five SSTRs and four ErbBs were variably expressed as both cell surface and cytoplasmic proteins. In both cell lines, SSTR4 and SSTR1 were highly expressed, followed by SSTR2 and SSTR5 with SSTR3 being the least expressed subtype, at the protein level. ErbBs were variably expressed with ErbB1 as the predominant subtype in both cell lines. ErbB1 is followed by ErbB3, ErbB2 and ErbB4 in MCF-7 at both the protein and mRNA levels. In MDA-MB-231 cells, ErbB1 is followed by ErbB2, ErbB4 and ErbB3. Our results indicate significant correlations at the level of mRNA and protein expression in a cell and receptor-specific manner. Using indirect immunofluorescence, we found that, in MCF-7 cells, SSTR5 was the most prominent subtype coexpressed with ErbBs followed by SSTR3, SSTR4, SSTR1 and SSTR2, respectively. In MDA-MB-231 cells, SSTR1 colocalized strongly with ErbBs followed by SSTR5, SSTR4, SSTR3 and SSTR2. ErbBs displayed higher levels of colocalization amongst themselves in MCF-7 cells than in MDA-MB-231 cells.

CONCLUSION

These findings may explain the poor response to endocrine therapy in ER-cancer. Differential distribution of SSTR subtypes with ErbBs in breast cancer cells in a receptor-specific manner may be considered as a novel diagnosis for breast tumors.

摘要

背景

生长抑素受体(SSTR)表达与肿瘤大小呈正相关,与表皮生长因子受体(ErbB)水平及肿瘤分化呈负相关。在本研究中,我们比较了两种乳腺癌细胞系:MCF-7(雌激素受体阳性)和MDA-MB-231(雌激素受体α阴性)中SSTR1-5及ErbB1-4的mRNA和蛋白表达情况。

结果

所有五种SSTR和四种ErbB均作为细胞表面和细胞质蛋白呈现不同程度的表达。在两种细胞系中,蛋白水平上,SSTR4和SSTR1高表达,其次是SSTR2和SSTR5,SSTR3是表达最少的亚型。ErbB以不同水平表达,在两种细胞系中ErbB1均为主要亚型。在MCF-7细胞中,蛋白和mRNA水平上,ErbB1之后依次是ErbB3、ErbB2和ErbB4。在MDA-MB-231细胞中,ErbB1之后依次是ErbB2、ErbB4和ErbB3。我们的结果表明,在细胞和受体特异性水平上mRNA和蛋白表达存在显著相关性。使用间接免疫荧光法,我们发现,在MCF-7细胞中,与ErbB共表达的最主要SSTR亚型是SSTR5,其次分别是SSTR3、SSTR4、SSTR1和SSTR2。在MDA-MB-231细胞中,与ErbB共定位最强的是SSTR1,其次是SSTR5、SSTR4、SSTR3和SSTR。与MDA-MB-231细胞相比,ErbB在MCF-7细胞中彼此之间共定位水平更高。

结论

这些发现可能解释了雌激素受体阴性癌症对内分泌治疗反应不佳的原因。乳腺癌细胞中SSTR亚型与ErbB以受体特异性方式的差异分布可被视为一种新型的乳腺肿瘤诊断方法。

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