Role of SIRT1 in Regulation of Epithelial-to-mesenchymal Transition in Breast Cancer Lymph Nodes Metastasis

Overview

Luminal A breast cancer is a kind of breast cancer with low rate lymph node metastasis and good survival. But in clinical practice, Luminal A breast cancer can present with early, unexpected lymph node metastasis some time, indicates poor survival. Silent information regulator 2 homolog 1 (SIRT1) plays a different role in breast cancer with different molecular typing. Previous study supports a role of SIRT1 protein as tumor suppressor in Luminal A breast cancer, in association with apoptosis-related proteins. The epithelial-to-mesenchymal transition(EMT) process results in loss of cell-cell adhesion, increased cell mobility, and is crucial for enabling the metastasis of cancer cells. But no similar study in Luminal A breast cancer. Hence, this study will 1) investigate the expression pattern of SIRT1 in primary tumor and lymph node metastasis; 2) investigate the different expression pattern of SIRT1 in T2/T3 , lymph node negative tumor and T1, lymph node positive tumor; 3) investigate potential role of SIRT1 enzyme in regulating cell migration and invasion in Luminal A breast cancer cells.

The study has three parts. 1. In large specimens of human Luminal A breast cancer with T1 tumor and positive axillary lymph node, study the difference expression of SIRT1 and related p53, Bcl-2, autophagy-related protein caspase-3, apaf-1 between primary tumor and lymph node metastases. Collect 50 pairs of T1 primary tumors and corresponding metastatic lymph node specimens. Using immunohistochemistry, anti-SIRT1, p53, Bcl-2, caspase-3 and apaf-1 antibody staining to identify the expression of above proteins in the primary tumor and lymph node metastases. 2. Eighty patients with Luminal type A breast cancer (T1N+) were enrolled in this study. At the same time,eighty patients were enrolled in the paraffin-embedded specimens of the patients with T2N+ and T3N+,too. And all patients were followed up. Immunohistochemical staining with anti-SIRT1, p53, Bcl-2, caspase-3, apaf-1, E-cadherin, N-cadherin, Vimentin antibodies to determine the relationship between above protein expression and routine clinicopathological and survival. 3. Explore the involvement of SIRT1 in hormone receptor-positive human breast cancer cells at the cellular level. The molecular mechanism of EMT-related protein regulation, which affects the proliferation, invasion and metastasis of tumor cells.