Autocrine growth hormone (hGH) and chemotherapeutic drug resistance in mammary carcinoma cells

Abstract

The purpose of this study was to identify possible mechanisms by which autocrine hGH may confer chemoresistance in breast cancer. A cellular model, a human mammary carcinoma cell line, MCF-7 cells, stably transfected with hGH gene or a translation-deficient hGH gene, was utilized in my study. As oxidative stress is a key mechanism of chemotherapeutic drugs, we demonstrated that autocrine hGH protects mammary carcinoma cells from oxidative stress induced cell death by p44/42 MAP kinase dependent transcriptional regulation of catalase. Secondly, profiling analysis of apoptotic proteins demonstrated upregulated anti-apoptotic protein Bcl-xl and decreased deactivation of anti-apoptotic protein Bcl-2 by autocrine hGH. Lastly, given that chemotherapeutic drugs could induce cell death by altering telomerase function, the results demonstrated that autocrine hGH induces telomerase activity by 3a??-UTR stabilization of hTERT mRNA. Therefore, the present study has demonstrated three different mechanisms by which autocrine hGH confer chemoresistance. This study suggests that antagonists of autocrine hGH may improve the efficacy of specific chemotherapeutic regimes in human mammary carcinoma.