FYN is overexpressed in human prostate cancer

Edwin M. Posadas, Hikmat Al-Ahmadie, Victoria L. Robinson, Ramasamy Jagadeeswaran, Kristen Otto, Kristen E. Kasza, Maria Tretiakov, Javed Siddiqui, Kenneth J. Pienta, Walter M. Stadler, Carrie Rinker-Schaeffer, Ravi Salgia

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To test the hypothesis that FYN, a member of the SRC family of kinases (SFKs), is up-regulated in prostate cancer, as FYN is functionally distinct from other SFKs, and interacts with FAK and paxillin (PXN), regulators of cell morphology and motility. MATERIALS AND METHODS: Through data-mining in Oncomine (http://www.oncomine.org), cell-line profiling with immunoblotting, quantitative reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemical analysis, we described FYN expression in prostate cancer. The analysis included 32 cases of prostate cancer, nine of prostatic intraepithelial neoplasia (PIN) and 19 normal prostates. Samples were scored for the percentage of stained glands and intensity of staining (from 0 to 3). Each sample was assigned a composite score generated by multiplying percentage and intensity. RESULTS: Data-mining showed an eight times greater FYN expression in prostate cancer than in normal tissue; this was specific to FYN and not present for other SFKs. Expression of FYN in prostate cancer cell lines (LNCaP, 22Rv1, PC3, DuPro) was detected using quantitative RT-PCR and immunoblotting. Expression of FYN and its signalling partners FAK and PXN was detected in human tissue. Comparing normal with cancer samples, there was a 2.1-fold increase in median composite score for FYN (P < 0.001) 1.7-fold increase in FAK (P < 0.001), and a doubling in PXN (P < 0.05). There was a 1.7-fold increase in FYN (P < 0.05) and a 1.6-fold increase in FAK (P < 0.01) in cancer compared with PIN. CONCLUSIONS: These studies support the hypothesis that FYN and its related signalling partners are up-regulated in prostate cancer, and support further investigation into the role of the FYN as a therapeutic target.

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalBJU International
Volume103
Issue number2
DOIs
StatePublished - Jan 2009
Externally publishedYes

Keywords

  • FAK
  • FYN
  • Paxillin
  • Prostate cancer
  • SRC

ASJC Scopus subject areas

  • Urology

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