title: Increased expression of ADAM12 and ADAM17 genes in laser-capture microdissected breast cancers and correlations with clinical and pathological characteristics.
abstract: ADAMs (a desintegrin and metalloprotease) are transmembrane glycoproteins involved in cell growth, differentiation, motility, and respectively, tumor growth and progression. Our aim was to evaluate ADAM12 spliced variants (ADAM12L - long membrane-bound and ADAM12S - secreted-short variant) and ADAM17 genes expression in breast cancers and to correlate their level of expression with clinical and pathological characteristics. Expression of ADAMs was analyzed using quantitative reverse-transcription polymerase chain reaction in laser-capture microdissected specimens of breast cancers and corresponding non-neoplastic breast tissues from 92 patients. The proteins' expression was confirmed by immunohistochemistry. Significantly elevated amounts of ADAM12L, ADAM12S and ADAM17 transcripts were found in malignant breast cells compared with normal breast tissue and both ADAMs proteins showed moderate to strong immunoexpression in tumor cells and peritumoral fibroblasts. ADAM12L and ADAM12S expressions were correlated with age, younger patients having higher expression of ADAM12L and ADAM12S; ductal cancers had higher expression of ADAM12L compared with lobular types, whereas ADAM12S was higher expressed in lobular cancers; higher expressions were found for both ADAM12 and ADAM17 in HER2/neu positive and highly proliferative cancers. High-grade cancers showed significantly increased expression of ADAM17. Our study on laser-capture microdissected specimens confers motivation for future work on development of ADAM-selective inhibitors for treatment of breast cancers.
authors.affiliation: Department of Biochemistry, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania. diana_narita@yahoo.com
authors.forename: Diana
authors.initials: D
authors.lastname: Narita
authors.forename: Edward
authors.initials: E
authors.lastname: Seclaman
authors.forename: Sorin
authors.initials: S
authors.lastname: Ursoniu
authors.forename: Andrei
authors.initials: A
authors.lastname: Anghel
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072199:ADAM12 Protein; D000072198:ADAM17 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D061346:Laser Capture Microdissection; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D047368:Tumor Burden
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human