Proliferation and apoptosis in PhIP-induced rat mammary gland carcinomas with elevated phosphotyrosine-STAT5a.
In the present study we addressed whether proliferation and apoptosis in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary gland carcinomas were different between carcinomas with high and low expression of phosphotyrosine (pY)-STAT5a. We determined that carcinomas with high pY-STAT5a were more proliferative (MIB5 immunostaining) and had a higher expression of cyclin D1 and estrogen receptor alpha. Furthermore, carcinomas with elevated pY-STAT5a demonstrated lower apoptosis as measured by the TUNEL assay and the Bcl-2 to Bax ratio, and showed increased expression of the long and short isoforms of the prolactin receptor. The results of this study are consistent with the notion that activated STAT5a may provide a growth advantage in some types of mammary gland cancers.
Papaconstantinou
Andriana D
AD
Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Snyderwine
Elizabeth G
EG
D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000633:toxicity*; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D019000:Phosphotyrosine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D002273:Carcinogens; D056741:Cyclin D; D016213:Cyclins; D047628:Estrogen Receptor alpha; D007093:Imidazoles; D050799:STAT5 Transcription Factor; C494094:Stat5a protein, rat; D051028:bcl-2-Associated X Protein; D019000:Phosphotyrosine; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine