Dominant-negative Stat5 inhibits growth and induces apoptosis in T47D-derived tumors in nude mice.
Signal transducer and activator of transcription 5 (Stat5) regulates growth, differentiation, and survival of mammary and hematopoietic cells. The role of Stat5 in breast cancer has not been established, although Stat5 is critical for some hematopoietic malignancies. In this study, we have analyzed the role of Stat5 in progression of the estrogen receptor-positive T47D human breast cancer cell line, in which Stat5b is constitutively activated. Expression of Stat5-regulated genes, such as cyclin D1 and bcl-xL, was strongly suppressed in T47D cells infected with the dominant-negative Stat5 adenovirus, AdStat5aDelta740. We also determined the phenotypic effects of introduction of dominant-negative Stat5 on T47D-derived tumors in nude mice. Tumors injected with AdStat5aDelta740 showed a 60% reduction in size, which was associated with the induction of apoptosis. Our results indicate the possibility of using dominant-negative Stat5 to induce apoptosis in certain Stat5-activated breast cancers.
Department of Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. hirokoy@med.nagoya-cu.ac.jp
Hiroko
H
Yamashita
Mariko
M
Nishio
Yoshitaka
Y
Fujii
Hirotaka
H
Iwase
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008894:Milk Proteins / Q000235:genetics* / Q000494:pharmacology*; D009374:Neoplasms, Experimental; D011960:Receptors, Estrogen; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011960:Receptors, Estrogen; D050799:STAT5 Transcription Factor; C494096:Stat5b protein, mouse; D015534:Trans-Activators