The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Phosphorylated Insulin-Like Growth Factor-I/Insulin Receptor Is Present in All Breast Cancer Subtypes and Is Related to Poor Survival
Open accessAbstract
Drugs that target the insulin-like growth factor-I receptor (IGF-IR) and/or insulin receptor (IR) are currently under investigation for a variety of malignancies including breast cancer. Although we have previously reported that IGF-IR expression in primary breast tumors is common, the activation status of this receptor has not been examined in relation to survival. Phosphorylated IGF-IR/IR (P-IGF-IR/IR) and its downstream signaling partner phospho-S6 (P-S6) were evaluated immunohistochemically in tumor tissue microarrays representing 438 cases of invasive breast cancer. P-IGF-IR/IR (n = 114; P = 0.046) and total levels of IR (n = 122; P = 0.009) were indicative of poor survival, whereas total IGF-IR (n = 112; P = 0.304) was not. P-IGF-IR/IR and P-S6 were coordinately expressed in primary breast tumors (likelihood ratio, 11.57; P = 6.70 × 10−4). Importantly, P-IGF-IR/IR was detected in all breast cancer subtypes (luminal, 48.1%; triple negative, 41.9%; and HER2, 64.3%). In vitro, the IGF-IR/IR inhibitor BMS-536924 decreased phospho-RSK and P-S6, and significantly suppressed the growth of breast cancer cell lines MCF-7, SUM149, and AU565 representing the luminal, triple negative, and HER2 subtypes, respectively, in monolayer and soft agar. BMS-536924 also inhibited growth in tamoxifen resistant MCF-7 Tam-R cells while having little effect on immortalized normal breast epithelial cells. Thus, we can determine which patients have the activated receptor and provide evidence that P-IGF-IR/IR is a prognostic factor for breast cancer. Beyond this, P-IGF-IR/IR could be a predictive marker for response to IGF-IR and/or IR-targeted therapies, as these inhibitors may be of benefit in all breast cancer subtypes including those with acquired resistance to tamoxifen. [Cancer Res 2008;68(24):10238–46]
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Self-citationInsulin-Like Growth Factor-I Receptor Signaling and Resistance to Trastuzumab (Herceptin)
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Self-citationRole and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction
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The role of insulin receptors and IGF-I receptors in cancer and other diseases
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Cited by
Giovannucci, E., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · Diabetes Care · doi:10.2337/dc10-0666 · Cited by 2,366
Self-citationThe hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418
The insulin and insulin-like growth factor receptor family in neoplasia: an update
Pollak, M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3215 · Cited by 1,116
Self-citationInsulin resistance and cancer risk: An overview of the pathogenetic mechanisms
Arcidiacono, B., Iiritano, S., Nocera, A., Possidente, K., Nevolo, M. T., Ventura, V., Foti, D., Chiefari, E., & Brunetti, A. (2012) · Experimental Diabetes Research · doi:10.1155/2012/789174 · Cited by 606
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer
Sparano, J. A., Gray, R. J., Ravdin, P. M., Makower, D. F., Pritchard, K. I., Albain, K. S., Hayes, D. F., Geyer, C. E., Dees, E. C., Goetz, M. P., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1904819 · Cited by 532
Metadata
- Authors
- Law, J. H., Habibi, G., Hu, K., Masoudi, H., Wang, M. Y. C., Stratford, A. L., Park, E., Gee, J. M. W., Finlay, P., Jones, H. E., Nicholson, R. I., Carboni, J., Gottardis, M., Pollak, M., & Dunn, S. E.
- Venue
- Cancer Research
- Published
- 2008-12-15
- Volume
- 68
- Issue
- 24
- Pages
- 10238-10246
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2079894826
- Cited by
- 401
- References
- 41
- FWCI
- 20.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Law, J. H., Habibi, G., Hu, K., Masoudi, H., Wang, M. Y. C., Stratford, A. L., Park, E., Gee, J. M. W., Finlay, P., Jones, H. E., Nicholson, R. I., Carboni, J., Gottardis, M., Pollak, M., & Dunn, S. E. (2008). Phosphorylated Insulin-Like Growth Factor-I/Insulin Receptor Is Present in All Breast Cancer Subtypes and Is Related to Poor Survival. Cancer Research. https://doi.org/10.1158/0008-5472.can-08-2755
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
