FYN is overexpressed in human prostate cancer.
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.


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.
Posadas
Edwin M
EM
Section of Hematology/Oncology, Department of Medicine, University of Chicago, IL, USA. eposadas@medicine.bsd.uchicago.edu
Al-Ahmadie
Hikmat
H
Robinson
Victoria L
VL
Jagadeeswaran
Ramasamy
R
Otto
Kristen
K
Kasza
Kristen E
KE
Tretiakov
Maria
M
Siddiqui
Javed
J
Pienta
Kenneth J
KJ
Stadler
Walter M
WM
Rinker-Schaeffer
Carrie
C
Salgia
Ravi
R
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051419:Paxillin / Q000378:metabolism; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C496061:PXN protein, human; D051419:Paxillin; C494957:FYN protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051076:Proto-Oncogene Proteins c-fyn