Vernimmen D, Gueders M, Pisvin S, Delvenne P, Winkler R
Molecular Oncology Laboratory, Experimental Cancer Research Center, Liège University, B-4000 Liège, Belgium.
Br J Cancer. 2003 Sep 1;89(5):899-906. doi: 10.1038/sj.bjc.6601200.
The ERBB2 gene is overexpressed in 30% of breast cancers and this has been correlated with poor prognosis. ERBB2 is upregulated in other cancers such as prostate, pancreas, colon and ovary. In breast cancer cells, the mechanisms leading to ERBB2 gene overexpression are increased transcription and gene amplification. In these cancers, AP-2 transcription factors are involved in ERBB2 overexpression, and AP-2 levels are correlated with p185(c-)(erbB-2) levels. In this work, we wanted to know if the same molecular mechanisms are responsible for the ERBB2 upregulation in non-breast cancers. We compared ERBB2 gene copy number, p185(c-)(erbB-2) and mRNA levels with AP-2 levels in several ovary, prostate, colon and pancreas cancer cells. A moderate expression of erbB-2 mRNA and protein were observed in some cells without gene amplification. In contrast to breast cancer cells, AP-2 factors were absent or low in some non-breast cells which did express ERBB2. It is thus likely that AP-2 is not a major player in the increased levels of erbB-2 transcripts in non-breast cancer cells. The transcriptional activity of the ERBB2 promoter in colon and ovary cancer cells was estimated using reporter vectors. The results showed that the promoter regions involved in ERBB2 gene overexpression in breast cancer cells are different from those that lead to the gene upregulation in colon and ovary cancers. In conclusion, our results indicate that different transcriptional and post-transcriptional mechanisms are responsible for the increased levels of erbB-2 transcript and protein in breast and non-breast cancer cells.
ERBB2基因在30%的乳腺癌中过度表达，这与预后不良相关。ERBB2在其他癌症如前列腺癌、胰腺癌、结肠癌和卵巢癌中也上调。在乳腺癌细胞中，导致ERBB2基因过度表达的机制是转录增加和基因扩增。在这些癌症中，AP - 2转录因子参与ERBB2的过度表达，且AP - 2水平与p185（c -）（erbB - 2）水平相关。在本研究中，我们想了解相同的分子机制是否导致非乳腺癌中ERBB2的上调。我们比较了几种卵巢癌、前列腺癌、结肠癌和胰腺癌细胞中ERBB2基因拷贝数、p185（c -）（erbB - 2）和mRNA水平与AP - 2水平。在一些没有基因扩增的细胞中观察到erbB - 2 mRNA和蛋白的适度表达。与乳腺癌细胞相反，一些表达ERBB2的非乳腺癌细胞中AP - 2因子缺失或水平较低。因此，AP - 2可能不是非乳腺癌细胞中erbB - 2转录本水平升高的主要因素。使用报告载体评估结肠癌和卵巢癌细胞中ERBB2启动子的转录活性。结果表明，乳腺癌细胞中导致ERBB2基因过度表达的启动子区域与结肠癌和卵巢癌中导致该基因上调的区域不同。总之，我们的结果表明，不同的转录和转录后机制导致乳腺癌和非乳腺癌细胞中erbB - 2转录本和蛋白水平升高。
