Role of Sox-9, ER81 and VE-cadherin in retinoic acid-mediated trans-differentiation of breast cancer cells.
Many aspects of development, tumor growth and metastasis depend upon the provision of an adequate vasculature. This can be a result of regulated angiogenesis, recruitment of circulating endothelial progenitors and/or vascular trans-differentiation. The present study demonstrates that treatment of SKBR-3 breast cancer cells with retinoic acid (RA), an important regulator of embryogenesis, cancer and other diseases, stimulates the formation of networks in Matrigel. RA-treatment of SKBR-3 cells co-cultured with human umbilical vein endothelial cells resulted in the formation of mixed structures. RA induces expression of many endothelial genes including vascular endothelial (VE) cadherin. VE-cadherin was also induced by RA in a number of other breast cancer cells. We show that RA-induced VE-cadherin is responsible for the RA-induced morphological changes. RA rapidly induced the expression of Sox-9 and ER81, which in turn form a complex on the VE-cadherin promoter and are required to mediate the transcriptional regulation of VE-cadherin by RA. These data indicate that RA may promote the expression of endothelial genes resulting in endothelial-like differentiation, or provide a mechanism whereby circulating endothelial progenitor cells could be incorporated into a growing organ or tumor.
Endo
Yoshimi
Y
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington DC, United States of America.
Deonauth
Kamla
K
Prahalad
Priya
P
Hoxter
Becky
B
Zhu
Yuelin
Y
Byers
Stephen W
SW
D015703:Antigens, CD / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D054338:Cell Transdifferentiation; D003094:Collagen / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000737:chemistry; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D003094:Collagen; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D006609:High Mobility Group Proteins; D007797:Laminin; D011509:Proteoglycans; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D014212:Tretinoin; D000099152:Cadherin 5; C095239:ETV1 protein, human; C527932:SOX9 protein, human; C059485:matrigel