Estrogen and insulin-like growth factor-I (IGF-I) independently down-regulate critical repressors of breast cancer growth
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Angelo J. Casa Adam S. Potter Simeen Malik ZaWaunyka Lazard Isere Kuiatse Hee-Tae Kim Anna Tsimelzon Chad J. Creighton Susan G. Hilsen
- چاپ و سال / کشور: 2011
Description
Although estrogen receptor alpha (ERa) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer, crosstalk between these pathways, particularly at the level of transcription, remains poorly understood. We performed microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3 or 24 h. IGF-I regulated mRNA of five to tenfold more genes than E2, and many genes were co-regulated by both ligands. Importantly, expression of these co-regulated genes correlated with poor prognosis of human breast cancer. Closer examination revealed enrichment of repressed transcripts. Interestingly, a number of potential tumor suppressors, for example, B-cell linker (BLNK), were down-regulated by IGF-I and E2. Analysis of three down-regulated genes showed that E2-mediated repression occurred independently of IGF-IR, and IGF-I-mediated repression occurred independently of ERa. However, repression by IGF-I or E2 required common kinases, such as PI3K and MEK, suggesting downstream convergence of the two pathways. In conclusion, E2 and IGF-I co-regulate a set of genes that affect breast cancer outcome. There is enrichment of repressed transcripts, and, for some genes, the down-regulation is independent at the receptor level. This may be important clinically, as tumors with active ERa and IGF-IR signaling may require co-targeting of both pathways.
Breast Cancer Res Treat DOI 10.1007/s10549-011-1540-0 Received: 16 April 2011 / Accepted: 19 April 2011
