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Updated: May 27, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Thyroid-specific knockout of the tumor suppressor mitogen-inducible gene 6 activates epidermal growth factor receptor
Chi-Iou Lin1, Justine A Barletta, Matthew A Nehs
1Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
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.
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