| First Author | Lin CI | Year | 2011 |
| Journal | Surgery | Volume | 150 |
| Issue | 6 | Pages | 1295-302 |
| PubMed ID | 22136853 | Mgi Jnum | J:196861 |
| Mgi Id | MGI:5490022 | Doi | 10.1016/j.surg.2011.09.014 |
| Citation | Lin CI, et al. (2011) Thyroid-specific knockout of the tumor suppressor mitogen-inducible gene 6 activates epidermal growth factor receptor signaling pathways and suppresses nuclear factor-kappaB activity. Surgery 150(6):1295-302 |
| abstractText | BACKGROUND: Mitogen-inducible gene 6 (Mig-6) is a putative tumor suppressor gene and prognostic biomarker in papillary thyroid cancer. We hypothesized that Mig-6 knockout would activate pro-oncogenic signaling in mouse thyrocytes. METHODS: We performed a thyroid-specific knockout using the Cre/loxP recombinase system. RESULTS: Four knockout and 4 control mouse thyroids were harvested at 2 months of age. Immunoblotting confirmed Mig-6 ablation in knockout mice thyrocytes. Epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK) phosphorylation levels were increased in Mig-6 knockout compared to wild-type mice. Total EGFR levels were similar in knockout and wild-type mice. However, EGFR was absent in the caveolae-containing membrane fraction of knockout mice, indicating that Mig-6 depletion is associated with a change in the membrane distribution of EGFR. Although p65 localized to the nucleus in wild-type mice, it was distributed in both cytoplasm and nucleus in knockouts, suggesting that Mig-6 loss decreases p65 activity. CONCLUSION: Our results confirm the feasibility of targeted, thyroid-specific gene knockout as a strategy for studying the relevance of specific genes in thyroid oncogenesis. We suggest that the loss of Mig-6 alters the membrane distribution of EGFR, which may limit receptor degradation and activate this oncogenic signaling pathway. |
