Homeodomain Interacting Protein Kinases Modulate Hypoxic Adaptation and Chemoresistance

Abstract

The goal of this project was to dissect the roles of Home domain Interacting Protein Kinases(HIPK) isoforms 2 and 3 in the development of castration resistant prostate cancer (PCa) following hypoxic reprogramming using established cell lines. Our objectives were to (1)ectopically express or silence HIPK2 and HIPK3 in PCa cell lines (LnCAP and LnCAP-abl) , (2)define the impact of HIPK manipulation on PCa cell biology (proliferation, apoptosis, metabolism, etc.), (3) evaluate the interplay of HIPK2 and HIPK3 with the Hippo signaling pathway, and (4) delineate the roles of HIPK2 and HIPK3 in PCa chemo-resistance. Our studies were able to demonstrate that HIPK2 was androgen responsive and under direct control of the androgen receptor. We were also able to clone HIPK2 and HIPK3 into expressing vectors and obtain small RNAs for silencing. Technical difficulties prevented our group from evaluating the impact on HIPKs in PCa as ectopic expression produced a protein of incorrect size and silencing proved ineffective. We will resolve these issue and continue to examine HIPKs inPCa in future studies.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2015
Accession Number
AD1032888

Entities

People

  • Jeremy W. Chambers
  • Myles Hodgson

Organizations

  • Florida International University

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Biomedical Research
  • Castration
  • Cell Biology
  • Cell Line
  • Cells
  • Department Of Defense
  • Electronic Mail
  • Information Operations
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Proteins

Fields of Study

  • Biology

Readers

  • Ballistic Missile Meteorology
  • Molecular Biology and Genetics
  • Prostate Cancer Biology.