Increased expression of ADAM family members in human breast cancer and breast cancer cell lines.
OBJECTIVE
ADAMs (A Disintegrin and Metalloprotease) are multifunctional, membrane-bound cell surface glycoproteins, which have numerous functions in cell growth, differentiation, and motility. We wished to investigate the expression of ADAM 9, 10, 12, 15, and in human breast cancer.


METHODS
Expression of ADAMs was determined in breast cancer specimens and the corresponding non-neoplastic breast tissue from 24 patients, and in the MCF-7 and MDA-MB 453 breast cancer cell lines via quantitative RT-PCR and immunohistochemistry. The effects of anti-ADAM antibodies on cell proliferation were assessed by measuring DNA-synthesis.


RESULTS
Breast cancer tissue samples showed increased mRNA expression of ADAM 9, 12, and 17, whereas ADAM 10 and 15 were not differently expressed. Protein expression was studied by immunohistochemistry. All ADAMs were expressed in MCF-7 and MDA-MB453 cell lines, with the highest expression levels being observed for ADAM 9, 12, and 17. Application of anti-ADAM 15 and anti-ADAM 17 antibodies significantly inhibited the proliferation of both MCF-7 and MDA-MB453 breast cancer cell lines. In contrast, the growth of MCF-7 cells appeared to be stimulated by the administration of anti-ADAM 12 antibody.


CONCLUSIONS
The results of this study suggest that ADAMs are differentially expressed in human breast cancer and are capable of modulating tumour cell growth.
Lendeckel
Uwe
U
Institute of Experimental Internal Medicine, Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany. uwe.lendeckel@medizin.uni-magdeburg.de
Kohl
Jana
J
Arndt
Marco
M
Carl-McGrath
Stacy
S
Donat
Hans
H
Röcken
Christoph
C
D051722:ADAM Proteins; D000072197:ADAM10 Protein; D000072199:ADAM12 Protein; D000072198:ADAM17 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry; D018275:Carcinoma, Lobular / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019483:Disintegrins / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis*; D008565:Membrane Proteins / Q000032:analysis; D008666:Metalloendopeptidases / Q000032:analysis*; D008875:Middle Aged; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D019483:Disintegrins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; C098660:ADAM15 protein, human; C098339:ADAM9 protein, human; D008666:Metalloendopeptidases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human