Expression and activity of transglutaminase II in spontaneous tumours of dogs and cats.
Tissue transglutaminase II (TGase II) is a dual function protein with both transamidating and guanidine triphosphate (GTP)-binding capabilities. Previous studies have implicated TGase as a pro-apoptotic molecule; however, our recent findings indicate that TGase II may act as a survival factor in various cell types. The purpose of this study was to survey TGase II expression in normal tissue and spontaneous tumours of dogs and cats, by Western blotting and immunohistochemistry. Bladder, liver and adrenal gland exhibited prominent expression of TGase II while other tissues, including mammary gland, displayed limited expression and activity. TGase II GTP-binding in normal tissues was proportional to the level of expression in all tissues examined. Normal mammary tissue and that showing benign hyperplasia did not express TGase II. However, 11/25 (44%) of canine mammary carcinomas and 10/12 (83%) of feline mammary carcinomas strongly expressed TGase II in either a stromal, cellular or combined pattern. The pattern of expression was not related to the classification of mammary carcinoma (solid, tubulopapillary, complex or anaplastic), except that two anaplastic canine mammary carcinomas showed prominent TGase II expression. Two canine mammary carcinoma cell lines showed prominent TGase expression, and when the TGase activity was inhibited, the cells became more sensitive to doxorubicin-induced cell death. Thus, TGase II was significantly expressed in mammary cancers from dogs and cats and immunoreactivity of TGase II was similar to that reported in humans beings. The pro-survival effect of TGase II in canine mammary carcinoma cell lines was similar to that previously reported in humans patients.
Wakshlag
J J
JJ
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, 14853 NY, USA.
McNeill
C J
CJ
Antonyak
M A
MA
Boehm
J E
JE
Fuji
R
R
Balkman
C E
CE
Zgola
M
M
Cerione
R A
RA
Page
R L
RL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western / Q000662:veterinary; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000662:veterinary*; D002415:Cats; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000662:veterinary; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000662:veterinary; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006965:Hyperplasia / Q000201:enzymology / Q000473:pathology / Q000662:veterinary; D008321:Mammary Glands, Animal / Q000201:enzymology* / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012189:Retrospective Studies; D011503:Transglutaminases / Q000378:metabolism*
D000970:Antineoplastic Agents; D004317:Doxorubicin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins