EXPRESSION OF C-MYC, C-HA-RAS1, AND C-ERBB-2 PROTO-ONCOGENES IN NORMAL AND MALIGNANT HUMAN-BREAST EPITHELIAL-CELLS
EXPRESSION OF C-MYC, C-HA-RAS1, AND C-ERBB-2 PROTO-ONCOGENES IN NORMAL AND MALIGNANT HUMAN-BREAST EPITHELIAL-CELLS
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DOI：
10.1093/jnci/81.22.1704
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发表时间：
1989-11-15
影响因子：
10.3
通讯作者：
SMITH, HS
中科院分区：
文献类型：
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作者：
BENZ, CC;SCOTT, GK;SMITH, HS
用短期培养的正常人乳腺上皮细胞来检测c-myc、c-Ha-ras1和c-erb B-2原癌基因在增殖正常细胞中的表达程度。这一水平的表达与原代肿瘤细胞、恶性渗出细胞或永久建立的乳腺癌细胞系进行了比较。从7种不同的乳房整形手术组织标本中制备的纯上皮样有机物质在短期组织培养中产生了增殖的正常上皮细胞。在每个样本中，原癌基因转录水平在短期培养上皮细胞时增加。这些水平经常超过从相同组织中测得的未培养有机物水平的10倍。在七个培养的正常乳腺样本中，有四个样本中至少有一个原癌基因的表达增加到了与增殖的乳腺癌细胞株MCF7相同或超过的水平。一个渗出性转移样本和两个原发性导管腺癌也被检测了原癌基因的表达。渗出性转移标本c-erbB-2信使RNA高表达，与其扩增的基因拷贝数一致，而原癌基因转录本在未经处理的肿瘤和未培养的器官中表达较低，但随着培养的肿瘤细胞的增殖而增加。这些结果表明，在乳腺活检标本中观察到的这些原癌基因的可变表达需要控制细胞生长速度或增殖指数。此外，这些发现表明，原癌基因的异常表达，而不是过度表达本身，需要被评估为促进人类乳腺癌发展的可能机制。
Short-term cultures of normal human mammary epithelial cells were used to determine the extent to which c-myc, c-Ha-ras1, and c-erbB-2 proto-oncogenes were expressed in proliferating normal cells. This level of expression was compared with that of primary tumor cells, malignant effusion cells, or permanently established breast cancer cell lines. Pure preparations of epithelial organoids from seven different reduction mammoplasty tissue samples yielded proliferating normal epithelial cells upon short-term tissue culture. In every sample, proto-oncogene transcript levels increased upon short-term culture of the epithelial cells. These levels often exceeded by 10-fold the levels measured in uncultured organoids from the same tissue. In four of the seven cultured normal breast samples, at least one of the proto-oncogenes increased its expression to a level equaling or exceeding that found in a proliferating breast cancer cell line, MCF7. One effusion metastasis sample and two primary ductal adenocarcinomas were also examined for proto-oncogene expression. The effusion metastasis sample expressed high levels of c-erbB-2 messenger RNA, in accord with its amplified gene copy number; otherwise, the levels of proto-oncogene transcripts were low in unprocessed tumor and uncultured organoids, but they increased with proliferation of the tumor cells in culture. These results indicate that the variable expression of these proto-oncogenes observed in breast biopsy specimens needs to be controlled for cellular growth rate or proliferation index. Furthermore, these findings suggest tht dysregulated proto-oncogene expression, rather than overexpression per se, needs to be evaluated as a possible mechanism contributing to the development of human brest cancer.