Restoration of Transforming Growth Factor Beta Signaling by Histone Deacetylase Inhibitors in Human Prostate Carcinoma
Abstract
The goal of the current grant is to investigate the potential antitumor activity of histone deacetylase inhibitor MS-275 along with the activation of TGFb signaling pathway with the restoration of TGFb receptor II. As presented in our initial proposal prostate cancer cell line LNCaP has reduced expression in TGFbRII which is due to the promoter histone deacetylation. Subsequent treatment with chromatin remodeling agent MS-275 was able to restore the expression of TGFbRII. We hypothesized that the restoration of TGFb signaling may contribute to the antitumor activity of MS-275. In the past a year and half we have focused our effort to identify the re-expression of TGFbRII in vivo and investigate the antitumor activity of MS- 275 in several relevant prostate cancer model. We observed dose and time dependent upregulation of TGFb1 and TGFbRII in LNCaP cells. A cDNA microarray of LNCaP cells (untreated vs. MS-275 treated) has been done and the data is being analyzed. We observed the antitumor activity of MS-275 in two different models of prostate cancer xenografts. Immunohistochemistry analysis of reactivation of TGFb1 in vivo is on going.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA463454
Entities
People
- Zheng D. Qian
Organizations
- Johns Hopkins University