PTHrP stimulates prostate cancer cell growth and upregulates aldo-keto reductase 1C3.

Abstract

The aim of the study was to demonstrate the role of parathyroid hormone related protein (PTHrP) in stimulating aldo-keto reductase (AKR) 1C3 expression in prostate cancer (CaP) cells. CaP cell proliferation and resistance to apoptosis was increased by PTHrP transfection. Conversely, reducing AKR1C3 expression by siRNA decreased cell proliferation. Since these effects could be mediated through AKR1C3-catalyzed reductions of the PPARγ ligand, 15-DeoxyΔ(12,14)-PGJ(2), we treated the cells with prostaglandins (PG). (PG) D(2) inhibited cell proliferation, but its metabolite, 9α,11β-PGF(2), did not effect CaP cell growth. The AKR1C family members serve as potential therapeutic targets for CaP therapy.

• Authors: Tracy M Downs, Douglas W Burton, Flavio L Araiza, Randolph H Hastings, Leonard J Deftos
• Journal: Cancer letters (Cancer Lett) Vol. 306 Issue 1 Pg. 52-9 (Jul 01 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21444150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Published by Elsevier Ireland Ltd.

Chemical References

• Androgens
• Parathyroid Hormone-Related Protein
• Prostaglandins
• 3-Hydroxysteroid Dehydrogenases
• Hydroxyprostaglandin Dehydrogenases
• AKR1C3 protein, human
• Aldo-Keto Reductase Family 1 Member C3

Topics

• 3-Hydroxysteroid Dehydrogenases (metabolism)
• Aldo-Keto Reductase Family 1 Member C3
• Androgens (metabolism)
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• Hydroxyprostaglandin Dehydrogenases (metabolism)
• Male
• Models, Biological
• Parathyroid Hormone-Related Protein (metabolism)
• Polymerase Chain Reaction (methods)
• Prostaglandins (metabolism)
• Prostatic Neoplasms (metabolism)
• Transfection
• Up-Regulation