ELUCIDATING THE FUNCTIONS OF TAp73 IN BREAST CANCER

Abstract

Our bioinformatics analyses and immunohistochemically staining results showed that TAp73 isoform was highly expressed in human breast cancer as compared to the normal tissue.

Therefore, this project aims to elucidate TAp73 functions in breast cancer development. Using three cell type-specific TAp73 knockout MMTV-PyMT mouse breast carcinoma mouse model, our results suggested that TAp73 can function as a tumor promoter in tumorigenic cells and as a tumor suppressor in cancer-associated fibroblast and tumor-associated macrophage. The PyMT mice with TAp73 knockout in the tumorigenic mammary epithelial cells had a longer latency in the development of the first palpable tumor, longer overall survivability, and had developed fewer lung metastases as compared to its littermate control. In contrast, the PyMT mice with TAp73 knockout specifically in the cancer-associated fibroblasts or the tumor-associated macrophages developed more lung metastases as compared to the control suggesting that TAp73 functions as a metastasis suppressor in the tumor microenvironment.