Regulation of T-cadherin by hormones, glucocorticoid and EGF

The cell adhesion molecule T-cadherin is an unusual member of the cadherin superfamily that lacks a cytoplasmic domain, binding instead to the cell membrane via a glycophosphatidyl inositol anchor. T-cadherin is a receptor for hexameric Acrp30/adiponectin and binds low-density lipoproteins in endothelial cells. T-cadherin is expressed widely in the brain and cardiovascular system, but expression is absent or decreased in several cancers. Little is known about the mechanisms and factors that control T-cadherin expression. Therefore, to investigate regulation of T-cadherin expression, we analysed 3.9 kb of the 5′-flanking region of human T-cadherin for promoter activity and identified potential transcription factor binding sites. Western blotting and a quantitative real-time RT-PCR assay developed for T-cadherin showed that estradiol, progesterone, EGF, dexamethasone and factors in serum were involved in transcriptional and post-transcriptional regulation of T-cadherin in human osteosarcoma cells; the effects observed were opposite to those described for T-cadherin's ligand, adiponectin. The data suggest that T-cadherin is regulated in a complex manner indicative of a role in hormone and drug-induced changes in bone morphology and pathology.