Botos Jeannine, Smith Roger, Kochevar Deborah T
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Exp Biol Med (Maywood). 2002 May;227(5):354-62. doi: 10.1177/153537020222700508.
Loss of or lowered retinoblastoma (Rb) expression has been included as a prognostic indicator in breast cancer. Low or no Rb expression is seen most commonly in high-grade breast adenocarcinomas, suggesting that a relationship may exist between loss of Rb and a less differentiated state, high proliferation rate, and high metastatic potential. In this study, we compared Rb function in two established breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, and in an established immortalized mammary epithelial cell line, MCF10A. Cells were synchronized in G0/G1 and were released for several durations, at which time total Rb protein, mRNA, and Rb/E2F/DNA complex formation were evaluated. Rb protein was significantly higher in the tumor cells than in MCF10A cells. However, Rb function was high for a longer duration in MCF10A cells as compared with MCF-7 and MDA-MB-231 cells. Our data support the general conclusion that Rb function, but not necessarily Rb protein, is lower in highly malignant breast adenocarcinoma cells as compared with lower grade tumor cells. These results emphasize the relevance of assessing Rb function over Rb protein. This is particularly important if Rb is to be used as a prognostic indicator for breast adenocarcinoma.
视网膜母细胞瘤(Rb)表达缺失或降低已被纳入乳腺癌的预后指标。Rb低表达或无表达最常见于高级别乳腺腺癌,这表明Rb缺失与低分化状态、高增殖率和高转移潜能之间可能存在关联。在本研究中,我们比较了两种已建立的乳腺腺癌细胞系MCF-7和MDA-MB-231以及一种已建立的永生化乳腺上皮细胞系MCF10A中的Rb功能。细胞在G0/G1期同步化,然后释放不同时长,此时评估总Rb蛋白、mRNA以及Rb/E2F/DNA复合物的形成情况。肿瘤细胞中的Rb蛋白显著高于MCF10A细胞。然而,与MCF-7和MDA-MB-231细胞相比,MCF10A细胞中Rb功能在较长时间内保持较高水平。我们的数据支持以下总体结论:与低级别肿瘤细胞相比,高恶性乳腺腺癌细胞中的Rb功能较低,但Rb蛋白不一定低。这些结果强调了评估Rb功能而非Rb蛋白的相关性。如果将Rb用作乳腺腺癌的预后指标,这一点尤为重要。