Breast Cancer Clinical Trial
Official title:
Role of SIRT1 in Regulation of Epithelial-to-mesenchymal Transition in Breast Cancer Lymph Nodes Metastasis for Luminal A Subtype
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.
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