Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is a major cause of mortality, largely as a consequence of metastases and transformation to androgen-independent growth. Metalloproteinases are implicated in cancer progression. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) are expressed in prostate cancer cells, with ADAMTS-1 and ADAMTS-15 being the most abundant. ADAMTS-15 but not ADAMTS-1 expression was downregulated by androgen in LNCaP prostate cancer cells, possibly through androgen response elements associated with the gene. ADAMTS-15 expression is predictive for survival in breast cancer, and the situation may be similar in prostate cancer, as androgen independence is usually due to aberrant signaling through its receptor.
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PMID:Androgen regulates ADAMTS15 gene expression in prostate cancer cells. 2059 Apr 45

Extracellular matrix remodeling has emerged as an important factor in many cancers. Proteoglycans, including versican (VCAN), are regulated via cleavage by the proteolytic actions of A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 motif (ADAMTS) family members. Alterations in the balance between Proteoglycans and ADAMTS enzymes have been proposed to contribute to cancer progression. Here, we analyzed the expression of ADAMTS-15 in human prostate cancer, and investigated the effects of enforced expression in prostate cancer cell lines. ADAMTS-15 was found to be expressed in human prostate cancer biopsies with evidence of co-localization with VCAN and its bioactive cleavage fragment versikine. Enforced expression of ADAMTS-15, but not a catalytically-inactive version, decreased cell proliferation and migration of the 'castrate-resistant' PC3 prostate cancer cell line in vitro, with survival increased. Analysis of 'androgen-responsive' LNCaP prostate cancer cells in vivo in NOD/SCID mice revealed that ADAMTS-15 expression caused slower growing tumors, which resulted in increased survival. This was not observed in castrated mice or with cells expressing catalytically-inactive ADAMTS-15. Collectively, this research identifies the enzymatic function of ADAMTS-15 as having a tumor suppressor role in prostate cancer, possibly in concert with androgens, and that VCAN represents a likely key substrate, highlighting potential new options for the clinic.
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PMID:ADAMTS-15 Has a Tumor Suppressor Role in Prostate Cancer. 3235 91