Androgens in breast cancer cells physiology A connection with calcium homeostasis
Year: 2012
Type: dissertation
Abstract: Several evidences suggest that androgenic actions and calcium (Ca2+) homeostasis alterations may contribute to the development of breast cancer. The androgen receptor is detected in the majority of human breast cancer cases, including those that are oestrogen and progesterone receptor negatives. It has also been shown that androgens play an important role regulating breast cells proliferation and death. On the other hand, it is known that intracellular Ca2+ is a ubiquitous second messenger involved in the regulation of several biological processes in the cell such as proliferation and apoptosis. In this way, deregulation of intracellular Ca2+ concentration via altered expression and/or function of Ca2+ transporters, Ca2+ channels and/or Ca2+ binding proteins may have implications breast pathophysiology. Recently, studies have demonstrated that androgens regulate the expression and/or activity of several Ca2+ regulator proteins, namely the Ca2+-binding protein regucalcin and voltage-dependent L-type Ca2+ channel in distinct cell types. The present project aims to investigate the effect of androgen 5α-dihydrotestosterone (DHT) on the expression of regucalcin and L-type Ca2+ channel (α1C subunit) in human breast cancer cells (MCF-7). The presence of regucalcin and L-type Ca2+ channel (α1C subunit) in these cells was confirmed by means of RT-PCR and Western Blot. The effect of androgens on the mRNA expression of regucalcin and L-type Ca2+ channel (α1C subunit) was evaluated by real-time PCR. DHT down-regulated the expression of regucalcin and L-type Ca2+ channel (α1C subunit) in MCF-7 cells. In both cases, this effect was reverted in presence of androgen inhibitor flutamide and oestrogen inhibitor ICI 182,780, suggesting that DHT effects regulating regucalcin and L-type Ca2+ channel (α1C subunit) expression are mediated by the androgen receptor, but also by the oestrogen receptor due to the metabolization of DHT to oestrogenic products. This study first demonstrated the presence of L-type Ca2+ channel (α1C subunit) in human breast cancer cells and showed that androgens modulate expression of Ca2+ regulator proteins in these cells. These findings suggest that androgenic actions regulating cell death and proliferation of breast cancer cells may be associated with the control of Ca2+ homeostasis.
Author: Carina Peres
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2188685865