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Publication : IGF-IR mediated mammary tumorigenesis is enhanced during pubertal development.

First Author  Jones RA Year  2014
Journal  PLoS One Volume  9
Issue  9 Pages  e108781
PubMed ID  25259518 Mgi Jnum  J:223493
Mgi Id  MGI:5649213 Doi  10.1371/journal.pone.0108781
Citation  Jones RA, et al. (2014) IGF-IR mediated mammary tumorigenesis is enhanced during pubertal development. PLoS One 9(9):e108781
abstractText  Although breast cancer typically develops in women over the age of 40, it remains unclear when breast cancer initiating events occur or whether the mammary gland is particularly susceptible to oncogenic transformation at a particular developmental stage. Using MTB-IGFIR transgenic mice that overexpress type I insulin-like growth factor receptor (IGF-IR) in a doxycycline-inducible manner, mammary tumorigenesis was initiated at different developmental stages. Tumor multiplicity was significantly increased while tumor latency was significantly decreased when the IGF-IR transgene was expressed during pubertal development compared to post-pubertal transgene expression. Moreover, metastatic spread of mammary tumors to the lungs was approximately twice as likely when IGF-IR was overexpressed in pubertal mice compared to post-pubertal mice. In addition, engraftment of pubertal MTB-IGFIR mammary tissue into cleared mammary fat pads of pubertal hosts produced tumors more frequently and faster than engraftment into adult hosts. These experiments show that the mammary microenvironment created during puberty renders mammary epithelial cells particularly susceptible to transformation.
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