Department of Biochemistry and Molecular Biology, Braman Family Breast Cancer Institute/Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, BRB Building, Room 723, 1501 N.W. 10th Avenue, Miami, FL 33136, USA.
Breast Cancer Res Treat. 2012 Feb;131(3):743-50. doi: 10.1007/s10549-011-1435-0. Epub 2011 Mar 12.
Yes-associated protein (YAP) is a well characterized transcriptional coactivator that interacts with various transcription factors and modulates their transcriptional activities. Phosphorylation of YAP by specific kinases regulates its cellular distribution and transcriptional activation functions. Sequestration of phosphorylated YAP in cytoplasm results in the reduction of transcription from its target genes. Since, YAP has been characterized as a coactivator of estrogen (ER) and progesterone (PR) receptors, we examined the immunohistochemical expression profile of YAP and correlation of YAP expression with that of ER and PR in normal (40 samples) and tumor breast (226 samples) from microarray tissue samples using immunohistochemistry. Here we show that YAP expression is significantly reduced in invasive carcinoma samples compared to normal breast tissues, which express high levels of YAP (YAP was positive for 45.1% of invasive carcinoma samples versus 82.5% of normal samples P < 0.0001). Furthermore, the data shows that reduced expression of YAP in invasive carcinoma samples is significantly associated with ER negativity (YAP was negative for 59.9% in ER negative versus 38.9% in ER positive invasive carcinoma samples, P = 0.007) and PR negativity (YAP was negative for 60.1% in PR negative versus 28.9% in PR positive, P = 0.0004). Among invasive carcinoma samples, 42.9% were YAP, ER, and PR negative, whereas only 7.5% were found to be YAP, ER, and PR positive. On the contrary, 20 out of 23 (87%) normal breast tissues that were positive for ER and PR were also positive for YAP. These data suggest that YAP may act as a tumor suppressor in invasive breast carcinomas and it can also be used as a molecular marker for ER and PR negative breast tumors.
Yes 相关蛋白（YAP）是一种经过充分研究的转录共激活因子，它与各种转录因子相互作用，并调节它们的转录活性。特定激酶对 YAP 的磷酸化调节其细胞分布和转录激活功能。磷酸化 YAP 在细胞质中的隔离导致其靶基因转录减少。由于 YAP 已被表征为雌激素（ER）和孕激素（PR）受体的共激活因子，我们使用免疫组织化学检查了来自微阵列组织样本的正常（40 个样本）和肿瘤乳房（226 个样本）中 YAP 的免疫组织化学表达谱，以及 YAP 表达与 ER 和 PR 表达的相关性。我们发现，与正常乳腺组织相比，浸润性癌样本中 YAP 的表达显著降低，正常乳腺组织中 YAP 的表达水平较高（YAP 在浸润性癌样本中的阳性率为 45.1%，而在正常样本中的阳性率为 82.5%，P<0.0001）。此外，数据显示，浸润性癌样本中 YAP 表达的降低与 ER 阴性显著相关（YAP 在 ER 阴性的浸润性癌样本中为阴性的占 59.9%，而在 ER 阳性的浸润性癌样本中为阴性的占 38.9%，P=0.007）和 PR 阴性（YAP 在 PR 阴性的浸润性癌样本中为阴性的占 60.1%，而在 PR 阳性的浸润性癌样本中为阴性的占 28.9%，P=0.0004）。在浸润性癌样本中，42.9%为 YAP、ER 和 PR 阴性，而只有 7.5%为 YAP、ER 和 PR 阳性。相反，23 个正常乳腺组织中有 20 个（87%）对 ER 和 PR 呈阳性，也对 YAP 呈阳性。这些数据表明，YAP 可能在浸润性乳腺癌中作为肿瘤抑制因子发挥作用，也可作为 ER 和 PR 阴性乳腺癌的分子标志物。
