ADAM15 disintegrin is associated with aggressive prostate and breast cancer disease.
The aim of the current study was to evaluate the expression of ADAM15 disintegrin (ADAM15) in a broad spectrum of human tumors. The transcript for ADAM15 was found to be highly upregulated in a variety of tumor cDNA expression arrays. ADAM15 protein expression was examined in tissue microarrays (TMAs) consisting of 638 tissue cores. TMA analysis revealed that ADAM15 protein was significantly increased in multiple types of adenocarcinoma, specifically in prostate and breast cancer specimens. Statistical association was observed with disease progression within clinical parameters of predictive outcome for both prostate and breast cancers, pertaining to Gleason sum and angioinvasion, respectively. In this report, we also present data from a cDNA microarray of prostate cancer (PCa), where we compared transfected LNCaP cells that overexpress ADAM15 to vector control cells. In these experiments, we found that ADAM15 expression was associated with the induction of specific proteases and protease inhibitors, particularly tissue inhibitor of metalloproteinase 2, as validated in a separate PCa TMA. These results suggest that ADAM15 is generally overexpressed in adenocarcinoma and is highly associated with metastatic progression of prostate and breast cancers.
Kuefer
Rainer
R
Department of Urology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109-0944, USA.
Day
Kathleen C
KC
Kleer
Celina G
CG
Sabel
Michael S
MS
Hofer
Matthias D
MD
Varambally
Sooryanarayana
S
Zorn
Christoph S
CS
Chinnaiyan
Arul M
AM
Rubin
Mark A
MA
Day
Mark L
ML
D051722:ADAM Proteins / Q000096:biosynthesis*; D000230:Adenocarcinoma / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014018:Tissue Distribution; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D018076:DNA, Complementary; D008565:Membrane Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D051722:ADAM Proteins; C098660:ADAM15 protein, human