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Protein 4.1B suppresses prostate cancer progression and metastasis

Academic Article
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Overview

authors

  • Wong, S. Y.
  • Haack, H.
  • Kissil, Joseph
  • Barry, M.
  • Bronson, R. T.
  • Shent, S. S.
  • Whittaker, C. A.
  • Crowley, D.
  • Hynes, R. O.

publication date

  • July 2007

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Protein 4.1B is a 4.1/ezrin/radixin/moesin domain-containing protein whose expression is frequently lost in a variety of human tumors, including meningiomas, non-small-cell lung cancers, and breast carcinomas. However, its potential tumor-suppressive function under in vivo conditions remains to be validated. In a screen for genes involved with prostate cancer metastasis, we found that 4.1B expression is reduced in highly metastatic tumors. Down-regulation of 4.1B increased the metastatic propensity of poorly metastatic cells in an orthotopic model of prostate cancer. Furthermore, 4.1B-deficient mice displayed increased susceptibility for developing aggressive, spontaneous prostate carcinomas. In both cases, enhanced tumor malignancy was associated with reduced apoptosis. Because expression of Protein 4.1B is frequently down-regulated in human clinical prostate cancer, as well as in a spectrum of other tumor types, these results suggest a more general role for Protein 4.1B as a negative regulator of cancer progression to metastatic disease.

subject areas

  • Adenocarcinoma
  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Disease Progression
  • Down-Regulation
  • Humans
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfilament Proteins
  • Neoplasm Metastasis
  • Prostatic Neoplasms
  • Tumor Suppressor Proteins
  • Xenograft Model Antitumor Assays
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Identity

PubMed Central ID

  • PMC1924789

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0705499104

PubMed ID

  • 17640904
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Additional Document Info

start page

  • 12784

end page

  • 12789

volume

  • 104

issue

  • 31

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