Down-regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity

Yu Zeng, Prakash Kulkarni, Takahiro Inoue, Robert H. Getzenberg

Research output: Contribution to journalArticle

Abstract

The microenvironment of the cancer cell is pivotal to its phenotypic regulation. One of the central components of the microenvironment is temperature. An elevation in environmental temperature has been shown to increase the cancer cell's susceptibility to chemo- and radiation therapy. The goal of the studies described here was to identify some of the pathways that are modified by a mild increase in temperature in cancer cells. Using prostate cancer cells as a model system we found that in addition to the well described and anticipated up-regulation of the heat shock family of proteins, there is a significant down-regulation of certain members of the "cold shock" family of proteins such as, RNA binding motif protein 3 (RBM3) and cold inducible RNA binding protein (CIRBP). siRNA-mediated down-regulation of the cold shock protein (CSP) encoding mRNAs dramatically attenuates cell survival in the absence of any heat application. Furthermore, we also demonstrate that knocking down the CSPs can enhance the therapeutic response of prostate cancer cells to chemotherapy. Our findings suggest that downregulating CSPs in cancer cells may "mimic" the stress response the cells experience when exposed to heat treatment rendering them more susceptible to therapy. Thus, the pharmacological modulation of RBM3 and CIRBP may represent novel therapeutic approaches for prostate cancer.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalJournal of Cellular Biochemistry
Volume107
Issue number1
DOIs
StatePublished - May 1 2009

Fingerprint

Cold Shock Proteins and Peptides
Neoplasm Genes
Cell Survival
RNA-Binding Proteins
Genes
Cells
Prostatic Neoplasms
Down-Regulation
Chemotherapy
Temperature
Hot Temperature
Cellular Microenvironment
Neoplasms
RNA
Tumor Microenvironment
Therapeutics
Heat-Shock Proteins
Radiotherapy
Small Interfering RNA
Up-Regulation

Keywords

  • Chemotherapy
  • Cold shock proteins
  • Prostate cancer

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Down-regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity. / Zeng, Yu; Kulkarni, Prakash; Inoue, Takahiro; Getzenberg, Robert H.

In: Journal of Cellular Biochemistry, Vol. 107, No. 1, 01.05.2009, p. 179-188.

Research output: Contribution to journalArticle

Zeng, Yu ; Kulkarni, Prakash ; Inoue, Takahiro ; Getzenberg, Robert H. / Down-regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity. In: Journal of Cellular Biochemistry. 2009 ; Vol. 107, No. 1. pp. 179-188.
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