Charles Sturt University
Graham Centre for Agricultural Innovation

Towards the role(s) of the putative membrane steroid hormone receptor PGRMC1 in breast cancer and in wider cell and organismal biology

Towards the role(s) of the putative membrane steroid hormone receptor PGRMC1 in breast cancer and in wider cell and organismal biology

Date :  Thursday, 11 December 2008
Time :  3.00pm
Venue : Conference Room, Wagga Wagga Agricultural Institute
Presenter : Dr Mike Cahill, Lecturer, School of Biomedical Sciences, Charles Sturt University

High sensitivity and wide resolution proteomics techniques were developed and used to measure protein abundance differences between breast cancer tumours that differed in estrogen receptor alpha (ER) status. This system was chosen because ER status represents one of the most important clinical criteria for therapy decisions. Patients with ER-negative tumours respond less well to chemotherapy, and have overall poorer prognoses. The protein PGRMC1 was found to differ in phosphorylation status between these tumours. Point mutations of specific potential PGRMC1 phosphorylation sites were made, and remarkably one mutant renders stable cell lines impervious to otherwise lethal doses of oxidative stress. Immune fluorescence analysis of breast tumours revealed that endogenous PGRMC1 is predominantly expressed in ER-negative cells, even in ER-positive tumours. Poorly oxygenated necrotic regions of advanced (comedo) tumours were surrounded by a halo of cells that co-expressed both PGRMC1 and the hypoxic marker Glut-1, which in turn was surrounded by another halo of ER-positive cells, suggesting a previously unsuspected role of PGRMC1 in hypoxic biology. These studies suggest various avenues by which PGRMC1 might modulate cell behaviour and survival: in cancer as well as in other biological systems where its involvement has been documented including e.g., neurogenesis and brain function, as well as the male and female mammalian reproductive systems.

Contact: Dr Mike Cahill , Email : mcahill@csu.edu.au

Phone: 02 6933 2729

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