Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis
- PMID: 18757322
- PMCID: PMC2654368
- DOI: 10.1200/JCO.2007.13.4429
Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis
Abstract
Purpose: Substantial evidence implicates insulin-like growth factor-I (IGF-I) signaling in the development and progression of breast cancer. To more clearly elucidate the role of IGF in human breast cancer, we identified and then examined gene expression patterns of IGF-I-treated breast cancer cells.
Methods: MCF-7 cells were stimulated with IGF-I for 3 or 24 hours and were profiled for greater than 22,000 RNA transcripts. We defined an IGF-I signature pattern of more than 800 genes that were up- or downregulated at both time points. The gene signature was examined in clinical breast tumors and in experimental models that represented other oncogenic pathways. The signature was correlated with clinical and pathologic variables and with patient outcome.
Results: IGF-I caused temporal changes in gene expression that were strongly associated with cell proliferation, metabolism, and DNA repair. Genes with early and sustained regulation by IGF-I were highly enriched for transcriptional targets of the estrogen receptor (ER), Ras/extracellular signal-related kinase 1/2, and phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathways. In three large, independent data sets of profiled human breast tumors, the IGF-I signature was manifested in the majority of ER-negative breast tumors and in a subset (approximately 25%) of ER-positive breast tumors. Patients who had tumors that manifested the IGF-I signature (including patients who did not receive adjuvant therapy) had a shorter time to a poor outcome event. The IGF gene signature was highly correlated with numerous poor prognostic factors and was one of the strongest indicators of disease outcome.
Conclusion: Transcriptional targets of IGF-I represent pathways of increased aggressiveness and possibly hormone independence in clinical breast cancers.
Figures
Comment in
-
Obesity and cancer treatment: weighing the evidence.J Clin Oncol. 2008 Sep 1;26(25):4060-2. doi: 10.1200/JCO.2008.17.4250. J Clin Oncol. 2008. PMID: 18757320 No abstract available.
Similar articles
-
Molecular regulation of phenolic compounds on IGF-1 signaling cascade in breast cancer.Food Funct. 2022 Mar 21;13(6):3170-3184. doi: 10.1039/d1fo03283f. Food Funct. 2022. PMID: 35253808 Review.
-
Favorable outcome associated with an IGF-1 ligand signature in breast cancer.Breast Cancer Res Treat. 2012 May;133(1):321-31. doi: 10.1007/s10549-012-1952-5. Breast Cancer Res Treat. 2012. PMID: 22297468
-
A gene transcription signature of obesity in breast cancer.Breast Cancer Res Treat. 2012 Apr;132(3):993-1000. doi: 10.1007/s10549-011-1595-y. Epub 2011 Jul 13. Breast Cancer Res Treat. 2012. PMID: 21750966
-
Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer.Breast Cancer Res. 2010;12(3):R40. doi: 10.1186/bcr2594. Epub 2010 Jun 22. Breast Cancer Res. 2010. PMID: 20569503 Free PMC article.
-
IGF-I and IGF-II expression in human breast cancer xenografts: relationship to hormone independence.Breast Cancer Res Treat. 1992;22(1):39-45. doi: 10.1007/BF01833332. Breast Cancer Res Treat. 1992. PMID: 1421423 Review.
Cited by
-
Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors.Nat Commun. 2024 Apr 30;15(1):3635. doi: 10.1038/s41467-024-47943-9. Nat Commun. 2024. PMID: 38688903 Free PMC article.
-
Regulation of IGF1R by MicroRNA-15b Contributes to the Anticancer Effects of Calorie Restriction in a Murine C3-TAg Model of Triple-Negative Breast Cancer.Cancers (Basel). 2023 Aug 29;15(17):4320. doi: 10.3390/cancers15174320. Cancers (Basel). 2023. PMID: 37686596 Free PMC article.
-
The Insulin-like Growth Factor Signaling Pathway in Breast Cancer: An Elusive Therapeutic Target.Life (Basel). 2022 Nov 29;12(12):1992. doi: 10.3390/life12121992. Life (Basel). 2022. PMID: 36556357 Free PMC article. Review.
-
Mini Review: Molecular Interpretation of the IGF/IGF-1R Axis in Cancer Treatment and Stem Cells-Based Therapy in Regenerative Medicine.Int J Mol Sci. 2022 Oct 4;23(19):11781. doi: 10.3390/ijms231911781. Int J Mol Sci. 2022. PMID: 36233084 Free PMC article. Review.
-
Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer.Cancers (Basel). 2022 Aug 12;14(16):3908. doi: 10.3390/cancers14163908. Cancers (Basel). 2022. PMID: 36010901 Free PMC article. Review.
References
-
- Pollak MN, Schernhammer ES, Hankinson SE: Insulin-like growth factors and neoplasia. Nat Rev Cancer 4:505-518, 2004 - PubMed
-
- Pollak M: Insulin-like growth factor physiology and cancer risk. Eur J Cancer 36:1224-1228, 2000 - PubMed
-
- Pollak M: IGF-I physiology and breast cancer. Recent Results Cancer Res 152:63-70, 1998 - PubMed
-
- Surmacz E: Function of the IGF-I Receptor in Breast Cancer. J Mammary Gland Biol Neoplasia 5:95-105, 2000 - PubMed
-
- Sachdev D, Yee D: Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther 6:1-12, 2007 - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical