Expression of cutaneous fatty acid-binding protein (C-FABP) in prostate cancer: potential prognostic marker and target for tumourigenicity-suppression

Int J Oncol. 2008 Apr;32(4):767-75.

Abstract

C-FABP or E-FABP is a metastasis inducing gene over expressed in human prostate carcinomas. To study its prognostic significance, an archival set of prostate tissues was analysed immunohistochemically. Levels of both nuclear and cytoplasmic C-FABP expression in carcinoma cells were significantly higher than those in normal and BPH tissues and the increased C-FABP was significantly associated with a reduced patient survival time. To test the therapeutic potential of targeting C-FABP, a clone (Si-clone-2) of cells was established by interfering C-FABP expression in highly malignant PC-3M cells. Suppression of C-FABP in cancer cells significantly inhibited their proliferation and tumourigenicity in vitro. When Si-clone-2 cells were orthotopically implanted into the prostate gland of mouse, 2/13 mice produced primary tumours with an average size of 23+/-5 mg, and no metastasis was produced in any of the 13 animals. Whereas in the control group, all 14 mice produced primary tumours with an average size of 1450+/-370 mg and 9/14 (64.3%) produced metastasis. When inoculated subcutaneously, all 5 mice inoculated with control cells developed tumours from day 4, with an average size of 1471+/-544 mm(3) at 5 weeks after the inoculation; whereas Si-clone-2 cells produced no tumours in any of the 5 animals at any time-point, indicating the suppression occurred at the initiation stage. Our results suggest that C-FABP may be used as a potential prognostic marker to predict patient outcome and the increased C-FABP expression is a possible target to inhibit the malignant progression of prostate cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Fatty Acid-Binding Proteins / analysis*
  • Fatty Acid-Binding Proteins / antagonists & inhibitors
  • Fatty Acid-Binding Proteins / genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Prognosis
  • Prostatic Neoplasms / chemistry*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / therapy
  • RNA, Small Interfering / pharmacology

Substances

  • Fatty Acid-Binding Proteins
  • RNA, Small Interfering