A recent study by researchers from the medical University of Bialystok in Poland has elucidated a novel regulatory role of estrogen on prolidase on HIF-1α in breast cancer cells.

Estrogen has been investigated in breast cancers for many years.  Estrogen-targeted therapy has shown some promise in treating estrogen receptor positive breast cancers.  Hypoxia inducible factors (HIFs) are transcription factors that are activated under conditions of cellular hypoxia.  HIFs are constituently inactivated in an oxygen-dependent manner and therefore become active in hypoxic conditions.  Angiogenesis is promoted by HIFs and therefore HIFs are of interest f or cancer researchers.

It seems that estrogen plays an important role in the degradation of collagen in the extracellular matrix (ECM); a necessary step for a cancer cell to achieve metastasis.  This breakdown necessitates the activity of metalloproteinases but the ultimate event is completed by cytoplasmic prolidase, through the release of hydroxyproline.

This study made use of MCF-7 cells (ER+,estrogen-dependent, receptors α and β) and MDA-MB-231 cells (ER-, estrogen-independent, β receptors only) to help determine specific estrogen activity.  It was shown that estrogen in MCF-7 cells promoted abundant prolidase activity.  In conditions without estrogen, the activity was markedly reduced.  In MDA-MB-231 cells, estrogen had no effect on prolidase activity.  Further, by examining both cell lines it was determined that the activity of HIF-1α was prolidase-dependent and reinforced the importance of the role of estrogen in the MCF-7 cells.

This study sheds light on two possible methods for fighting breast cancer: in ER+ breast cancers, the estrogen receptor could be a useful target.  In ER- breast cancers, ECM enzymes, in this case prolidase, could be a potential target for therapy.

The original research paper was published in: Molecular and Cellular Biochemistry, July 2013, Volume 379, Issue 1-2, pp 29-36.

The effect of estrogen on prolidase-dependent regulation of HIF-1α expression in breast cancer cells.

This study used StressMarq Biosciences HIF-1α monoclonal antibody, product# SMC-184, in western blotting and confocal microscopy bio-imaging.