Increased expression of the metastasis-associated gene Ehm2 in prostate cancer.
BACKGROUND
Alterations of fibroblast growth factors and their receptors contribute to prostate cancer progression by enhancing cell survival, motility, and proliferation. The expression of the FGFR-4 Arg(388) variant is correlated with the occurrence of pelvic lymph node metastasis and biochemical (PSA) recurrence in men undergoing radical prostatectomy. Ehm2 is an androgen-regulated gene that has been associated with metastasis in other systems, so we sought to determine if it is expressed in prostate cancer and if the FGFR-4 Arg(388) variant can increase its expression.


METHODS
Expression of Ehm2 was examined by quantitative RT-PCR and Western blotting in prostate cell lines and by quantitative RT-PCR, in situ hybridization, and immunohistochemistry in prostate tissues. The effect of Ehm2 expression on collagen IV adhesion was tested by transient overexpression and RNA interference.


RESULTS
Ehm2 expression is upregulated in prostate cancer cell lines and prostate cancer tissues. Expression of the FGFR-4 Arg(388) variant results in increased expression of Ehm2. Increased expression of Ehm2 leads to decreased adhesion to collagen IV, which has been associated with metastasis in cancers. Analysis of tissue microarrays revealed that increased Ehm2 expression is associated with biochemical recurrence after radical prostatectomy, which is indicative of more aggressive disease.


CONCLUSIONS
Ehm2 is overexpressed in prostate cancer and may enhance disease progression and metastasis.
Wang
Jianghua
J
Department of Pathology of Baylor College of Medicine and Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, Texas 77030, USA.
Cai
Yi
Y
Penland
Rebecca
R
Chauhan
Sanjay
S
Miesfeld
Roger L
RL
Ittmann
Michael
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D009364:Neoplasm Recurrence, Local; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D015854:Up-Regulation
D003598:Cytoskeletal Proteins; C478965:EPB41L4B protein, human; D013196:Dihydrotestosterone; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4