Enhanced GBX2 expression stimulates growth of human prostate cancer cells via transcriptional up-regulation of the interleukin 6 gene.
Previous studies demonstrated that the GBX2 homeobox gene is consistently overexpressed in cultured human prostate cancer cell lines. In this study, the human GBX2 cDNA was cloned and a quantitative reverse transcription-PCR method used to demonstrate that GBX2 mRNA expression is enhanced in approximately 70% of human prostate cancer tissues compared with normal human prostate tissues. Purified recombinant GBX2 protein binds specifically to an ATTA motif within the promoter of the interleukin 6 (IL-6) gene. Using an antisense approach, down-regulation of the expression of GBX2 correlated with decreased expression of IL-6 and an inhibition of tumorigenicity of PC3 human prostate cancer cells. In addition, in vitro growth of the antisense clones was partially restored by exogenous addition of recombinant IL-6 protein to the culture media. These data demonstrated that enhanced GBX2 expression results in a stimulation of malignant growth of prostate cancer cells and that part of this stimulation involves up-regulation in the transcription of the IL-6 gene.
Gao
A C
AC
University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. gaoac@msx.upmc.edu
Lou
W
W
Isaacs
J T
JT
D000818:Animals; D002455:Cell Division; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
C084958:GBX2 protein, human; C513182:Gbx2 protein, mouse; D018398:Homeodomain Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins