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

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).

To audit the potential cross-talk between TGF-β and the molecular distribution of hormone receptors (ERs and PR).

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.

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.

It is concluded that SMAD3 can promote cell proliferation and metastases in (ERα+, ERβ+) and PR+ breast cancer.