ADAM12 and ADAM17 gene expression in laser-capture microdissected and non-microdissected breast tumors.
ADAM (a disintegrin and metalloprotease)12 and ADAM17 are multidomain transmembrane proteins involved in ectodomain shedding of cytokines, growth factors and adhesion molecules, with pivotal activities in the tumor microenvironment. The aim of this study was to confirm the up-regulation of ADAM17 and ADAM12 gene splicing variants in breast tumors and to delineate their expression between laser-capture microdissected (LCM) and non-microdissected breast tumors. The gene expression was analyzed by quantitative-reverse transcription-PCR in a total sample of 109 breast tumors paired with corresponding non-neoplastic breast tissues. ADAM12 and 17 proteins expression for corresponding tissue samples was confirmed by immunohistochemistry. ADAM12S, 12L and 17 genes were significantly up-regulated in either malign or benign LCM samples when compared to non-tumor controls. For non-LCM samples, it was obtained also an increased expression for ADAM12 and 17 genes in cancers, while in benign tumors only ADAM12 variants were significantly up-regulated compared to controls. When benign versus malignant tumors were compared, in LCM samples all investigated genes displayed a higher expression in cancers, whereas in non-LCM, ADAM12 variants were overexpressed in benign samples. The increased expression of ADAM12 protein in the tumor cells and stroma of benign breast diseases was immunohistochemically confirmed. These differences between LCM and non-LCM samples were explained by the contribution of the stroma to the expression of this marker. This study underlines the accuracy conferred by homogenous LCM samples on gene expression profiles and confers further evidence regarding the role of ADAM12 and 17 in the breast tumorigenesis and progression.
Department of Biochemistry, University of Medicine and Pharmacy Victor Babes, Eftimie Murgu Square No 2A, 300041 Timisoara, Romania. diana_narita@yahoo.com
Diana
D
Narita
Edward
E
Seclaman
Razvan
R
Ilina
Natalia
N
Cireap
Sorin
S
Ursoniu
Andrei
A
Anghel
D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072199:ADAM12 Protein; D000072198:ADAM17 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D042282:Microdissection; D008875:Middle Aged; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
Lab Invest. 2005 Jan;85(1):154-9
15543203
Cancer Cell. 2006 Jul;10(1):39-50
16843264
Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1034-42
18483323
Cancer Sci. 2007 May;98(5):621-8
17355265
Clin Cancer Res. 2006 Dec 15;12(24):7359-68
17189408
Int J Cancer. 2003 Jul 20;105(6):754-61
12767059
J Biol Chem. 2008 Nov 14;283(46):31920-32
18801731
Cancer Biol Ther. 2006 Jun;5(6):648-56
16627988
J Biol Chem. 2006 Apr 7;281(14):9418-22
16455653
Prenat Diagn. 2003 Dec 30;23(13):1086-91
14691998
Am J Physiol Cell Physiol. 2006 Jul;291(1):C1-10
16769815
Mol Aspects Med. 2008 Oct;29(5):258-89
18762209
Int J Cancer. 2008 Jun 1;122(11):2634-40
18241035
Clin Cancer Res. 2009 Feb 15;15(4):1140-4
19228719
J Biol Chem. 2004 Oct 8;279(41):42898-906
15292243
Am J Pathol. 2003 Dec;163(6):2191-9
14633594
Curr Pharm Des. 2009;15(20):2300-10
19601832
J Cell Biol. 2007 Feb 26;176(5):695-707
17325209
J Cell Sci. 2007 Mar 15;120(Pt 6):943-52
17344430
Neoplasia. 2006 Apr;8(4):319-29
16756724
EMBO J. 2003 Mar 3;22(5):1114-24
12606576
Science. 2006 Oct 13;314(5797):268-74
16959974
Cancer Res. 2005 Jun 1;65(11):4754-61
15930294
Nat Rev Cancer. 2006 Jul;6(7):506-20
16794634
Int J Biochem Cell Biol. 2008;40(9):1685-702
18342566
Am J Pathol. 2004 Nov;165(5):1743-53
15509542
Ann Oncol. 2008 Jun;19(6):1075-81
18238782
J Biol Chem. 2000 Jun 16;275(24):18574-80
10849447
Cancer Metastasis Rev. 2006 Mar;25(1):57-68
16680572
Science. 1996 Nov 8;274(5289):998-1001
8875945
Nat Rev Mol Cell Biol. 2005 Jan;6(1):32-43
15688065
J Clin Pathol. 2000 Sep;53(9):666-72
11041055
J Cancer Res Clin Oncol. 2005 Jan;131(1):41-8
15565459
Lab Invest. 2007 Sep;87(9):951-62
17643124
Hepatology. 2003 May;37(5):1056-66
12717386
Methods. 2001 Dec;25(4):402-8
11846609
J Biol Chem. 2004 Dec 3;279(49):51323-30
15381692
J Cell Biol. 2007 Jul 16;178(2):201-8
17620406
J Cell Biol. 2000 May 29;149(5):1143-56
10831617
Int J Mol Med. 2003 Apr;11(4):449-53
12632096
Oncogene. 2000 Dec 27;19(56):6642-50
11426650
Nat Rev Cancer. 2008 Dec;8(12):929-41
19005493
Mol Biol Cell. 2007 Jan;18(1):176-88
17079736
Nat Protoc. 2006;1(2):586-603
17406286
Clin Cancer Res. 2007 Mar 15;13(6):1892-902
17363546
Oncogene. 2006 Aug 31;25(39):5462-6
16607276