| First Author | Jones RA | Year | 2009 |
| Journal | Oncogene | Volume | 28 |
| Issue | 21 | Pages | 2152-62 |
| PubMed ID | 19377512 | Mgi Jnum | J:151349 |
| Mgi Id | MGI:4353577 | Doi | 10.1038/onc.2009.79 |
| Citation | Jones RA, et al. (2009) Reversibility and recurrence of IGF-IR-induced mammary tumors. Oncogene 28(21):2152-62 |
| abstractText | 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. |
