Characterization of Regucalcin as a new target in prostate pathophysiology: an androgen-regulated gene involved in the modulation of cell cycle and apoptosis

Researchers from the Health Sciences Research Centre of the University of Beira Interior (CICS-UBI), which previously described the calcium-binding protein, Regucalcin (RGN), as an underexpressed gene in prostate adenocarcinoma comparatively to non-neoplastic prostate or benign prostate hyperplasia cases, developed a study aiming at investigate the role of this protein in the modulation of cell cycle and apoptosis pathways in rat prostate. In this work, recently published in The prostate journal, the research group led by Sílvia Socorro suggests that RGN plays a role modulating the expression of target regulators of these pathways, which indicates the involvement of this protein maintaining the cell survival and death balance in prostatic tissues. Furthermore, this work has demonstrated that RGN is an androgen-target gene in rat prostate, which supports its relevant function in prostatic physiology.

Authors and Affiliations:

Cátia V. Vaz, Cláudio J. Maia, Ricardo Marques, Inês M. Gomes, Sara Correia, Marco G. Alves, José E. Cavaco, Pedro F. Oliveira and Sílvia Socorro

CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal

Abstract:

BACKGROUND. Regucalcin (RGN) is a calcium (Ca²⁺)-binding protein underexpressed in prostate adenocarcinoma comparatively to non-neoplastic prostate or benign prostate hyperplasia cases. Moreover, RGN expression is negatively associated with the cellular differentiation of prostate adenocarcinoma, suggesting that loss of RGN may be associated with tumor onset and progression. However, the RGN actions over the control of prostate cell growth have not been investigated.

METHODS. Androgens are implicated in the promotion of prostate cell proliferation, thus we studied the in vivo effect of androgens on RGN expression in rat prostate. The role of RGN modulating cell proliferation and apoptotic pathways in rat prostate was investigated using transgenic animals (Tg-RGN) overexpressing the protein.

RESULTS. In vivo stimulation with 5a-dihydrotestosterone (DHT) down-regulated RGN expression in rat prostate. Cell proliferation index and prostate weight were reduced in Tg- RGN, which was concomitant with altered expression of cell-cycle regulators. Tg-RGN presented diminished expression of the oncogene H-ras and increased expression of cell-cycle inhibitor p21. Levels of anti-apoptotic Bcl-2, as well as the Bcl-2/Bax protein ratio were increased in prostates overexpressing RGN. Both caspase-3 expression and enzyme activity were decreased in the prostates of Tg-RGN.

CONCLUSIONS. Overexpression of RGN resulted in inhibition of cell proliferation and apoptotic pathways, which demonstrated its role maintaining prostate growth balance. Thus, deregulation of RGN expression may be an important event favoring the development of prostate cancer. Moreover, the DHT effect down-regulating RGN expression in rat prostate highlighted for the importance of this protein in prostatic physiology.

Jornal:

The Prostate

Link:

http://onlinelibrary.wiley.com/doi/10.1002/pros.22835/abstract