New Action of Inhibin Alpha Subunit in Advanced Prostate Cancer

Abstract

This project ultimately aims to identify the role of inhibin alpha (INHA) in advanced prostate cancer. The hypothesis to be tested is that INHA is tumor promoting and pro-metastatic in advanced prostate cancer. To date, we have made significant progress towards understanding the role INHA in advanced prostate disease. We have demonstrated that increased INHA expression in highly aggressive, metastatic and androgen-independent prostate cancer cell line, PC3, further promotes its tumor growth and metastatic ability. Increase in metastasis was further evident by increase lymph vessel density (LVD) and lymphatic invasion by the cancer cells. This was also accompanied by increase in VEGF-A and VEGF-C expression. Furthermore, we conducted a cross-sectional study to determine a link between INHA expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and VEGF-R3 expression which are well established prognostic factors of PCa. Elevated expression of INHA in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. This study is the first to demonstrate a pro-tumorigenic and pro-metastatic role for INHA in the androgen-independent stage of metastatic prostate disease. Our results also suggest that INHA expression in the primary prostate tumor can be used as a predictive factor for prognosis of PCa. Our preliminary work on understanding the mechanism suggests the involvement of ERK/MAPKsignaling pathway through which INHA promotes tumor growth and metastasis. Whatever the outcomes of these experiments are, we are sure to contribute significantly to our understanding of the role of INHA in the process of prostate carcinogenesis.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2009
Accession Number
ADA502296

Entities

People

  • Preetika Balanathan

Organizations

  • Monash University

Tags

DTIC Thesaurus Topics

  • Androgens
  • Biomedical Research
  • Cancer
  • Cell Line
  • Cells
  • Diseases And Disorders
  • Gene Expression
  • Health Services
  • Lymph Nodes
  • Lymphatic System
  • Lymphatic Vessels
  • Metastasis
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Statistical Analysis
  • Tissues

Fields of Study

  • Medicine

Readers

  • Military Engineering.
  • Oncology and Biomarker-Based Cancer Detection.
  • Prostate Cancer Biology.