Modulation of Beta-catenin Activity With PKD1 Prostate Cancer

Abstract

During 2008-09 funding period we made considerable progress on our grant proposal and published one paper in Molecular Cancer Therapeutics. Our research findings were considered for highlight and appeared on cover page (cover illustration, MCT September 2008, volume 7). Along with publication three more papers were published from the lab. In next funding cycle we are expected to make progress on remaining specific aims and to have couple more publications. In brief, in 2008-09 funding period we have investigated the effect of bryostatin on PKD1 expression, beta-catenin transcription, cell proliferation, and cellular aggregation. In this study we examined the effect of Bryostatin 1 treatment on PKD1 activation, beta-catenin translocation and transcription activity and malignant phenotype of prostate cancer cells. Initial activation of PKD1 with Bryostatin 1 leads to colocalization of the cytoplasmic pool of beta-catenin with PKD1, trans-Golgi network markers and proteins involved in vesicular trafficking. Activation of PKD1 by Bryostatin 1 decreases nuclear beta-catenin expression and beta-catenin/TCF transcription activity. Activation of PKD1 alters cellular aggregation and proliferation in prostate cancer cells associated with subcellular redistribution of E-cadherin and beta-catenin. For the first time, we have identified Bryostatin 1 modulates beta-catenin signaling through PKD1, which identifies a novel mchansim to improve efficacy of Bryostatin 1 in clinical setting.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2009
Accession Number
ADA502884

Entities

People

  • Meena Jaggi
  • Subhash C. Chauhan

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biomedical Research
  • Cancer
  • Cell Line
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Confocal Microscopy
  • Golgi Apparatus
  • Intercellular Junctions
  • Modulation
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Proteins
  • Therapy

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular and Cellular Biology
  • Prostate Cancer Biology.