Clinicopathological and Functional Analysis of Hormone Related Gene in Breast Cancer

乳腺癌组织中雌激素受体(ER)α和孕激素受体（PgR）水平的检测对区分激素依赖型和非激素依赖型肿瘤具有重要意义。然而，ERβ及其辅助因子在乳腺癌发生和发展中的重要作用仍有待阐明。为了评估这些因素在内分泌治疗应答中的临床意义，我们采用免疫组化（IHC）和/或定量实时逆转录- pcr方法检测了原发性乳腺癌组织中ERα/β、PgR、aib1和NcoR1的表达。描述了一种用于定量乳腺肿瘤中ERa和PR的免疫组化方法，并显示出与内分泌治疗的相对反应性良好相关。乳腺癌肿瘤中ERβ的高表达与乳腺癌患者的预后相关，IHC和real-time PCR方法均显示了这一点。ERβ变体ERβcx表达改变的意义尚不清楚。由于aib1的表达随乳腺癌的发生而升高，且与ER活性相关，我们检测了aib1的mRNA和蛋白水平，发现ERα与aib1 mRNA之间没有相关性。然而，与未显示aib1核染色的乳腺肿瘤患者相比，aib1核表达阳性的乳腺肿瘤患者倾向于对激素治疗有反应。也有证据表明，在er α阳性的小肿瘤中，NCOR1 mRNA的表达更高，而高表达的患者生存率更高，对他莫昔芬的反应性也更好。ATBF1-A是位于16q22-24的肿瘤抑制基因，也是乳腺癌的预后因素。ATBF1-A的表达可能是乳腺癌内分泌治疗的预测因素。

The assessment of the estrogen receptor (ER)α and the progesterone receptor (PgR) in breast cancer tissues is important for discriminating between hormone-dependent and hormone-independent tumors. However, the substantial roles of ERβ and co-factors in the development and progression of breast cancer remain to be elucidated.To evaluate the clinical significance of these factors in the response to endocrine therapy, we investigated the expressions of ERα/β, PgR, AIB 1 and NcoR1 in primary breast cancer tissues using immunohistochemistry (IHC) and/or quantitative real-time reverse transcription-PCR.An IHC method for quantifying ERa and PR in breast tumors was described, and shown to correlate well with the relative responsiveness to endocrine therapy. Higher expression of ERβ in breast tumors correlated with better prognosis of breast cancer patients, and this was shown using both IHC and real-time PCR methodologies. The significance of altered expression of an ERβ variant, ERβcx was unclear. Since AIB 1 expression in increased with breast cancer and correlates with ER activity, mRNA and protein levels of AIB 1 were measured and no correlation between ERα and AIB 1 mRNA was found. However, patients with breast tumors that stained positively for nuclear AIB 1 expression tended to respond to hormone therapy as compared to patients with breast tumors that did not show nuclear staining of AIB 1. Evidence was also presented suggesting that NCOR1 mRNA expression is higher in small, ERα-positive tumors, and those patients with higher expression exhibited better survival and responsiveness to tamoxifen.ATBF1-A is a tumor suppress gene located in 16q22-24 and also have a prognostic factor in breast cancer. ATBF1-A expression might have the ability of predictive factor of endocrine therapy in breast cancer.