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Title:
Reversibility and recurrence of IGF-IR-induced mammary tumors | Oncogene
Description:
The type-I insulin-like growth factor receptor (IGF-IR) is frequently overexpressed in breast cancer and therapeutic agents targeting IGF-IR are currently in development. The ultimate success of anti-IGF-IR therapies will depend on the extent to which established tumors remain dependent upon IGF-IR signaling for sustained growth. To investigate the potential benefits and pitfalls of targeting IGF-IR, we used a doxycycline inducible mouse model of IGF-IR initiated breast cancer. We found that downregulation of IGF-IR results in tumor-size-dependent regression to an undetectable state. Partially regressed tumors almost always resumed growth in the absence of doxycycline and a proportion of tumors that regressed to an undetectable state ultimately recurred. This re-emergence of tumor growth in the absence of doxycycline was facilitated by IGF-IR-dependent and IGF-IR-independent mechanisms. Tumor escape from IGF-IR dependence was associated with an epithelial to mesenchymal transition and upregulation of transcriptional repressors of E-cadherin. These results suggest that tumors initiated by IGF-IR have the ability to become independent of this initiating oncogene, and IGF-IR independence is associated with characteristics consistent with an epithelial to mesenchymal transition.
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nature portfolio permissions reprints privacy policy nature formalin-fixed paraffin-embedded tissues cancer research society tgf-beta-induced collagen expression c-myc-induced mammary adenocarcinomas advertising igf-ir-induced mammary tumors social media health research p19arf/p53 pathway lesions author information authors mammary gland development anti-igf-ir therapies real-time pcr primer conditional wnt-induced tumorigenesis targeting igf-ir author correspondence tumor-size-dependent regression endocrine-responsive breast cancer springerlink instant access personal data recombinant humanized anti-insulin tumor development igf-ir-independent mechanisms signal transduction function regulates epithelial plasticity data protection permissions invasive breast cancers transgenic mouse model igf-ir-dependent e-cadherin gene expression accelerates mammary tumorigenesis breast cancer cells kinase activity human breast cancer igf-ir dependence igf-ir independence human lung tumors igf-ir signaling igf-ir results growth factor receptor breast cancer panagiotis induces tumor formation metastasizing mammary carcinomas igf-ii mrna privacy
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headline:Reversibility and recurrence of IGF-IR-induced mammary tumors
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