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 TGF beta. We show that Cyr61 transcription is activated by TGF beta and that the human Cyr61 promoter contains consensus sequences that bind Smad proteins. TGF beta in the tumor microenvironment may stimulate cancer metastases to sites such as bone by increasing Cyr61 expression and secretion. (c) 2006 Elsevier Ireland Ltd. All rights reserved.