Baskari Srinivas, Govatati Suresh, Madhuri Vijaya, Nallabelli Nayudu, K Paul Marx, Naik Srinivas, Balka Swarna, Tamanam Raghava Rao, Devi Venkata Ramana
1 Department of Biochemistry, Osmania University, Hyderabad, India.
2 Department of Biochemistry, Andhra University, Visakhapatnam, India.
Tumour Biol. 2017 Oct;39(10):1010428317719121. doi: 10.1177/1010428317719121.
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.
乳腺癌的进展通常取决于激素，其中人类生长激素在乳腺癌进展中起着重要作用。早期研究报道了核因子-κB的组成性激活，核因子-κB是乳腺癌中生长激素受体介导的信号通路的关键调节因子，但其确切的分子机制仍不清楚。在本研究中，我们调查了人类生长激素对乳腺癌细胞核因子-κB激活和上皮-间质转化的影响。我们的结果表明，人类生长激素的自分泌产生通过激活核因子-κB（65 kDa）和下调E-钙黏蛋白表达来增强细胞增殖。此外，核因子-κB表达的增强显著增加了MCF-7细胞系中的细胞增殖并减少了细胞凋亡。核因子-κB表达的增加显著增强了自分泌人类生长激素刺激的乳腺癌细胞迁移和侵袭，这导致了MCF-7细胞的上皮-间质转化。总之，我们的研究揭示了人类生长激素对乳腺癌细胞核因子-κB活性和上皮-间质转化的影响。我们的发现将有助于理解“生长激素-核因子-κB轴”在乳腺癌发生中的分子作用，这可能有助于发现适合疾病治疗的通路抑制剂。
