Stromal remodelling is required for progressive involution of the rat ventral prostate after castration: identification of a matrix metalloproteinase-dependent apoptotic wave

• Grant number: 09/15316-8
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: November 01, 2009
• End date: October 31, 2011
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Hernandes Faustino de Carvalho
• Grantee: Hernandes Faustino de Carvalho
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Prostate epithelial-cell apoptosis occurs in response to androgen deprivation. We have hypothesized that continued regression would require stromal changes. Studying apoptosis kinetics up to the 14th day after castration, we identified succesive waves of apoptosis, with a prominent peak on day 11. This peak was associated with caspase-3 activity, nuclear translocation of apoptosis-inducing factor (AIF), and clusterin expression. The apoptosis peak on day 11 was preceded by increased MMP-2 and MMP-7 activation, and MMP-9 expression on days 9 and 10. Treatment with the MMP inhibitors doxycyclin, hydrocortisone, or GM6001 caused significant reduction in the apoptosis rate on day 11. The present data demonstrate that prostatic epithelial-cell deletion at the 11th day after castration was induced by focal degradation of the extracellular matrix associated with stromal remodeling. (AU)