SMAD3, Cell proliferation and lymph nodes metastasis in breast cancer hormone-dependent.

Abstract

INTRODUCTION: Tumor Growth Factor-β (TGF-β) is a multifunctional cytokine that plays a crucial role in various biological processes. TGF-β is also involved in various pathologies including breast cancer (BC). BC is strongly dependent on hormone receptors such as Estrogen receptors (ERa, ERb) and Progesterone Receptor (PR). AIM: To audit the potential cross-talk between TGF-β and the molecular distribution of hormone receptors (ERs and PR). METHODS: The current study analyzes the expression patterns of SMAD3, ERα, ERβ and PR in 40 breast tumor tissues using qRT-PCR. Furthermore, the Ki-67 and HER2/neu status have been detected by Immunohistochemistry. RESULTS: Our results show a decrease in the SMAD3 expression in 27 of the 40 cases while its expression is increased in the remaining 13 cases (p=0.003). The over-expression of SMAD3 is associated with high tumor grades. Moreover, there is a significant positive correlation between SMAD3+ with a high proliferative index and metastases (p=0.001 and p=0.01respectevely). The SMAD3 expression relative to (ERα, ERβ) subgroups shows a significant association of SMAD3+ with the (ERα+, ERβ+) subgroups (p=0.009). The same is true for PR, our results show a significant association of SMAD3+ with PR+ (p=0.02). Moreover, analysis of the expression of molecular subgroups (SMAD3+, ERα+, ERβ+) and (SMAD3+, PR+) compared to clinical and pathological information shows a significant association with high grade tumors, a high proliferation index (p=0.02, p= 0.01 respectively) and lymph node infiltration. CONCLUSION: It is concluded that SMAD3 can promote cell proliferation and metastases in (ERα+, ERβ+) and PR+ breast cancer.