Her2 is important to androgen receptor expression and phosphorylation in estrogen receptor negative breast cancer cells

• Main Authors: Chen-Chuan Huang, 黃振權
• Other Authors: Ho Lin
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/02307786426144897010

碩士 === 國立中興大學 === 生命科學系所 === 100 === According to the statistics data, breast cancer is a leading cancer in Taiwan. There are about 2,000 people die of breast cancer every year, and the number of deaths has increased steadily. It is important to find out how does breast cancer begin, develop and metastasis. There are several methods for breast cancer treatment: like surgery, chemotherapy, radiotherapy, hormone therapy and target therapy. Because of the development in molecular biology, we can find the subtle changes by gene chip and analyze which gene is much more active in breast cancer, this gene will be the major target in the treatment of breast cancer, so called target therapy. In the recent studies, Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal growth factor receptor-2 (Her2) has become the major targets in the treatment of breast cancer. Triple-negative breast cancer (TNBC) accounts for approximately 12%~20% of breast cancers. This subtype of breast cancer lacks expression ER, PR and Her2. TNBC is a poor prognostic factor for disease-free and overall survival; no effective specific targeted therapy is readily available for TNBC. Therefore, to find new molecular target becomes an important research topic, androgen receptor (AR) is one of them. Here we want to discuss the role of AR in breast cancer. The MTT assay and cell counting assay show that AR activation decreased the cell proliferation of MDA-MB-453 cells. it might through the increase of p27 protein level to down-regulation cell cycle. On the other hand, Her2 activation could down-regulate the AR Serine81 phosphorylation and decrease AR protein level. In our previous study, Serine81 (Ser81) is the highest stoichiomertric phosphorylation site on AR and involes in stabilization of AR. Knockdown Her2 expression by siRNA could increase the AR protein level. Use the Her2 inhibitor, Lapatinib also found increases of both AR Ser81 phosphorylation and p27 protein level . All the data show that Her2 is important to androgen receptor expression and phosphorylation in estrogen receptor negative breast cancer cells MDA-MB-453. Finally, we hope to understand the understanding of AR in breast cancer, can contribute to the diagnosis and treatment of breast cancer.