Accession Number:

ADA626126

Title:

Seminal Plasma Proteins as Androgen Receptor Corregulators Promote Prostate Cancer Growth

Descriptive Note:

Annual rept. 23 Sep 2014-22 Sep 2015

Corporate Author:

JOHNS HOPKINS UNIV BALTIMORE MD

Personal Author(s):

Report Date:

2015-10-01

Pagination or Media Count:

20.0

Abstract:

We hypothesized that semenogelins, especially semenogelin I SgI in the presence of zinc, promote prostate cancer growth via functioning as androgen receptor AR co-activators. Using cell lines stably expressing SgI, we investigated biological functions of SgI in prostate cancer. Zinc, without SgI, inhibited cell growth of both AR-positive and AR-negative lines. Co-expression of SgI prevented zinc inhibiting androgen-mediated proliferation of AR-positive cells, whereas SgI andor androgen showed marginal effects in AR-negative cells. Culture in the conditioned medium containing secreted forms of SgI failed to significantly increase cell viability with or without zinc. Similar effects of SgI overexpression on androgen-induced cell invasion, such as its significant enhancement with zinc, were seen. Overexpression of SgI also augmented androgen-mediated prostate-specific antigen mRNA, protein in the presence of zinc. In luciferase assays, SgI showed even slight inhibitory effects at 0 microM zinc and significant stimulatory effects at 100 microM zinc on androgen-enhanced AR transactivation. Using coimmunoprecipitation, we demonstrated androgen-induced physical interactions between AR and SgI. These results suggest that intracellular SgI, together with zinc, functions as an AR co-activator and thereby promotes androgen-mediated prostate cancer progression. We further found that SgI did not interact with other steroid hormone receptors, including estrogen receptors and glucocorticoid receptor, and did not significantly affect AR NC-terminus interactions. More importantly, the LxxLL motif Lleucine xany amino acids present in SgI is likely to be essential and sufficient for mediating the interaction with AR.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE