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Increased expression of the metastasis‐associated gene Ehm2 in prostate cancer
Author(s) -
Wang Jianghua,
Cai Yi,
Penland Rebecca,
Chauhan Sanjay,
Miesfeld Roger L.,
Ittmann Michael
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20474
Subject(s) - prostate cancer , metastasis , pca3 , prostate , medicine , cancer research , prostatectomy , cancer , tissue microarray , pathology , immunohistochemistry , oncology , biology
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. Prostate 66: 1641–1652, 2006. © 2006 Wiley‐Liss, Inc.