Influence of autocrine growth hormone on NF-κB activation leading to epithelial–mesenchymal transition of mammary carcinoma

Abstract

Progression of breast cancers often depends on hormones among which human growth hormone is prominently involved in breast cancer progression. Earlier studies have reported constitutive activation of nuclear factor-κB, a key regulator of growth hormone receptor–mediated signaling pathway in breast carcinoma, but the precise molecular mechanisms are still elusive. In this study, we investigated the effect of human growth hormone on nuclear factor-κB activation and epithelial–mesenchymal transition in breast carcinoma. Our results explored that autocrine production of human growth hormone enhances cellular proliferation by the activation of nuclear factor-κB (65 kDa) and downregulation of E-cadherin expression. Furthermore, enhanced nuclear factor-κB expression significantly increases cell proliferation and diminishes apoptosis in MCF-7 cell line. Increased expression of nuclear factor-κB significantly enhances mammary carcinoma cell migration and invasion stimulated by autocrine human growth hormone, which results in epithelial–mesenchymal transition of MCF-7 cells. In conclusion, our study revealed the influence of human growth hormone on nuclear factor-κB activity and epithelial–mesenchymal transition in mammary carcinoma. Our findings will help to understand molecular role of “growth hormone–nuclear factor-κB axis” in mammary carcinogenesis which may facilitate the discovery of suitable pathway inhibitors for disease treatment.