title: IGF-IR mediated mammary tumorigenesis is enhanced during pubertal development.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Jones
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Watson
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada.
authors.forename: Craig I
authors.initials: CI
authors.lastname: Campbell
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Moorehead
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D012741:Sexual Maturation / Q000502:physiology*
chemical_list: D017526:Receptor, IGF Type 1