RT Journal Article
SR Electronic
T1 Reduced Lysyl Oxidase Messenger RNA Levels in Experimental and Human Prostate Cancer
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 1285
OP 1290
VO 58
IS 6
A1 Ren, Chengzhen
A1 Yang, Guang
A1 Timme, Terry L.
A1 Wheeler, Thomas M.
A1 Thompson, Timothy C.
YR 1998
UL http://cancerres.aacrjournals.org/content/58/6/1285.abstract
AB To identify genes associated with prostate cancer progression, we developed a strategy involving the use of differential display PCR and a panel of genetically matched primary tumor- and metastasis-derived mouse prostate cancer cell lines. We analyzed sequences that were differentially stimulated by transforming growth factor-β1 in primary tumor-versus metastasis-derived cell lines, based on our previous studies indicating that acquisition of differential responses to this growth factor could result in phenotypic traits that facilitate tumor metastasis from specific cell clones within the primary tumor. Using this system, we isolated and sequenced a cDNA fragment that encoded mouse lysyl oxidase (LO) and was induced by transforming growth factor-β1 in primary tumor but not in metastasis-derived cells. Northern blotting analysis revealed increased LO expression in a panel of primary tumor cell lines but significantly reduced or nondetectable expression in their matched metastatic counterparts. Further in situ hybridization analysis revealed LO expression in normal mouse prostate epithelium but, in most cases, progressive loss of expression in primary prostate cancer and associated metastatic lesions. Importantly, in situ hybridization studies of normal human prostate and prostate malignancies revealed a similar loss of expression during progression to metastasis. The progressive loss of LO expression during prostate cancer progression provides information that may increase our understanding of the mechanisms that underlie this disease. In addition, LO may provide a useful molecular marker and/or establish a novel therapeutic target for prostate cancer. ©1998 American Association for Cancer Research.