Insulin receptor substrate-1 regulates the transformed phenotype of BT-20 human mammary cancer cells. Cancer Res 2007 Mar 01;67(5):2124-30
Date
03/03/2007Pubmed ID
17332342DOI
10.1158/0008-5472.CAN-06-3954Scopus ID
2-s2.0-33947286775 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
Although originating from a human breast cancer, BT-20 cells do not form colonies in soft agar. BT-20 cells do not express insulin receptor substrate-1 (IRS-1), which is known to promote both normal and abnormal growth and to inhibit differentiation. Stable expression of IRS-1 confers to BT-20 cells the ability to form colonies in soft agar. BT-20 cells form tumors in xenografts in mice, but the size of tumors is twice as large when the cells express IRS-1. The increased transformed phenotype is characterized by occupancy of the rDNA and cyclin D1 promoters by IRS-1 and the activation of the cyclin D1, c-myc, and rDNA promoters. In addition, the retinoblastoma protein, which is detectable in the rDNA promoter of quiescent BT-20/IRS-1 cells, is replaced by IRS-1 after insulin-like growth factor-I stimulation. Our results indicate that in BT-20 human mammary cancer cells, expression of IRS-1 activates promoters involved in cell growth and cell proliferation, resulting in a more transformed phenotype. Targeting of IRS-1 could be effective in inhibiting the proliferation of mammary cancer cells.
Author List
Dalmizrak O, Wu A, Chen J, Sun H, Utama FE, Zambelli D, Tran TH, Rui H, Baserga RMESH terms used to index this publication - Major topics in bold
AnimalsBreast Neoplasms
Cell Transformation, Neoplastic
Chromatin Immunoprecipitation
Female
Genes, bcl-1
Genes, myc
Humans
Insulin Receptor Substrate Proteins
Mice
Mice, Nude
Neoplasm Transplantation
Phenotype
Phosphoproteins
Promoter Regions, Genetic
Retinoblastoma Protein
