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 a with the activation of TGFb signaling pathway with the restoration of TGFbeta 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 half, we have focused our effort to identify the re-expression of TGFbRII in vivo, and investigate the antitumor activity 275 in several relevant prostate cancer model. We observed dose and time dependent upregulation of TGFbeta1 and TC 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.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2005
Accession Number
ADA457563

Entities

People

  • Zheng D. Qian

Organizations

  • Johns Hopkins University

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Biomedical Research
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Dna Microarrays
  • Enzyme Inhibitors
  • Growth Factors
  • Inhibition
  • Inhibitors
  • Microarray Analysis
  • Neoplasms
  • Peptide Growth Factors
  • Peptides
  • Prostate
  • Prostate Cancer
  • Xenografts

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).