| Autor: |
Casa AJ; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA., Potter AS, Malik S, Lazard Z, Kuiatse I, Kim HT, Tsimelzon A, Creighton CJ, Hilsenbeck SG, Brown PH, Oesterreich S, Lee AV |
| Jazyk: |
angličtina |
| Zdroj: |
Breast cancer research and treatment [Breast Cancer Res Treat] 2012 Feb; Vol. 132 (1), pp. 61-73. Date of Electronic Publication: 2011 May 04. |
| DOI: |
10.1007/s10549-011-1540-0 |
| Abstrakt: |
Although estrogen receptor alpha (ERα) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer, cross-talk 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 ERα. 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 ERα and IGF-IR signaling may require co-targeting of both pathways. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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