The human Cyr61 gene is a transcriptional target of transforming growth factor beta in cancer cells.
Cyr61 is a multifunctional protein that can stimulate angiogenesis and tumor growth. Its expression by many cancers and breast cancers increases with tumor grade. Cyr61 is closely related to connective tissue growth factor, CTGF. Both proteins regulate skeletal development, suggesting that they could contribute to breast cancer metastases to bone, a process regulated by TGFbeta. We show that Cyr61 transcription is activated by TGFbeta and that the human Cyr61 promoter contains consensus sequences that bind Smad proteins. TGFbeta in the tumor microenvironment may stimulate cancer metastases to sites such as bone by increasing Cyr61 expression and secretion.
Bartholin
Laurent
L
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Aurbach Medical Research Building, Charlottesville, VA 22908, USA.
Wessner
Lisa L
LL
Chirgwin
John M
JM
Guise
Theresa A
TA
D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor; D055515:Cysteine-Rich Protein 61; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C501848:CCN1 protein, human; C526317:CCN2 protein, human; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D051785:Smad Proteins; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D008156:Luciferases