Fas-Fas ligand signaling pathway mediates an interleukin-12-induced rejection of a murine prostate tumor system

Shaobo Zhang, Guangyuan Zeng, Chinghai Kao, Thomas Gardner, Christopher Sweeney, Ning Sun Yang, John N. Eble, Liang Cheng

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

BACKGROUND. Recent data suggest that anti-tumor activities of interleukin-12 (IL-12) involve the induction of apoptosis. Fas (APO-1/CD95) is a type I membrane protein that is capable of initiating an apoptosis signaling pathway when bound to its ligand (FasL). We undertook this study to test the hypothesis that Fas-FasL -mediated apoptosis plays a role in IL-12-induced tumor regression. METHODS. An mIL-12 expression vector driven by cytomegalovirus promoter was used to express murine IL-12 cDNA in the RM-9 murine prostate carcinoma cell line. Control RM-9 cells and RM-9 cells stably transfected with IL-12 gene (RM-9-IL12) were inoculated subcutaneously in 4- to 6-week-old male C57BL/J6 mice. Tumor size was measured every 3 days. Western blot and immunohistochemical assays were used to evaluate Fas and FasL protein expression. In situ fluorescent end labeling was used to label apoptotic cells. RESULTS. IL-12-expressing RM-9 prostate carcinoma cells transplanted into C57BL/J6 mice grew more slowly than control RM-9 cells and vector control RM-9-Luc cells. The average survival time of the RM-9-IL12 mice was longer than 53 days, whereas the mean survival for mice transplanted with control RM-9 cells was only 16 days. Apoptotic cells were more numerous in RM-9-IL12 tumors: 10.3% vs. 1.5% in control (P = 0.001). Fas and FasL proteins were increased approximately twofold in the RM-9-IL12 tumors compared with the RM-9 control tumors as determined by Western blot and immunohistochemical analyses (P < 0.05). CONCLUSION. The Fas-FasL-mediated apoptosis pathway may contribute to the IL-12-induced rejection of prostate carcinoma.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalProstate
Volume53
Issue number1
DOIs
StatePublished - Sep 15 2002

Keywords

  • Apoptosis
  • Fas
  • Fas ligand
  • Interleukin-12
  • Prostate

ASJC Scopus subject areas

  • Urology

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