Yin Yang-1 inhibits tumor cell growth and inhibits p21WAF1/Cip1 complex             formation with cdk4 and cyclin D1.
The GLI-Krüppel zinc finger factor yin yang-1 (YY1) is a complex protein that regulates a variety of processes including transcription, proliferation, development and differentiation. YY1 inhibits cell growth in a cell type-specific manner. The role played by YY1 in its control of tumor cell growth is unclear and controversial. We show here that YY1 can suppress the growth of different tumor cell types in vitro, including human breast carcinoma cells and glioblastoma cells. YY1 also blocked the growth of 13762 MAT mammary adenocarcinoma isografts in rats. YY1 inhibited 13762 MAT tumor growth by approximately 80% compared with the GFP alone group 21 days after injection. YY1 inhibited proliferating cell nuclear antigen (PCNA) expression and pRbSer249/Thr252 phosphorylation without influencing tumor microvascular density. Moreover, YY1 inhibited p21WAF1/Cip1 complex formation with cdk4 and cyclin D1. These findings demonstrate that YY1 can negatively regulate the growth of multiple malignant cell types.
Centre for Vascular Research, University of New South Wales,                     Sydney, Australia.
Hideto
H
Ishii
Mark D
MD
Hulett
Jian-Mei
JM
Li
Fernando S
FS
Santiago
Christopher R
CR
Parish
Levon M
LM
Khachigian
D000230:Adenocarcinoma / Q000098:blood supply / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055806:Microvessels / Q000473:pathology; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D047368:Tumor Burden; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
C530106:Ccnd1 protein, rat; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D050986:YY1 Transcription Factor; D019938:Cyclin D1; D049452:Green Fluorescent Proteins; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4