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.
Bromhead
Collette
C
Medical Laboratory Wellington, Wellington, New Zealand. cbromhead@medlabwellington.co.nz
Miller
John H
JH
McDonald
Fiona J
FJ
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D002522:Chlorocebus aethiops; D003907:Dexamethasone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology; D011374:Progesterone / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis
D015820:Cadherins; D005938:Glucocorticoids; C099972:H-cadherin; D006728:Hormones; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D008156:Luciferases