Disruption of transforming growth factor-β signaling in thyroid follicular epithelial cells or intrathyroidal fibroblasts does not promote thyroid carcinogenesis.

Mika Shimamura, Mami Nakahara, Tomomi Kurashige, Kazuaki Yasui, Masahiro Nakashima, Yuji Nagayama

Endocrine journal 2014

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Transforming growth factor β (TGF-β) members, pleiotropic cytokines, play a critical role for carcinogenesis generally as a tumor suppressor in the early cancer development, but as a tumor promoter in the late stage of cancer progression. The present study was designed to clarify the role for TGF-β signaling in early thyroid carcinogenesis using the conditional Tgfbr2(floxE2/floxE2) knock-in mice, having 2 loxP sites at introns 1 and 2 of Tgfb2r gene. When these mice were crossed with thyroid peroxidase (TPO)-Cre or fibroblast-specific protein-1 (FSP1)-Cre, the resultant mice, Tgfbr2(tpoKO) and Tgfbr2(fspKO), lost TGF-β II receptor expression (thereby TGF-β signaling) specifically in the thyroid follicular epithelial cells or fibroblasts, respectively. The thyroid morphology was monitored up to 52 weeks in these mice, showing no tumor development, except one Tgfbr2(tpoKO) mouse developing follicular adenoma like-lesion. Our data suggest that TGF-β signaling in mesenchymal or follicular epithelial cells of the thyroid does not appear to function as a tumor suppressive barrier at the early stage of thyroid carcinogenesis.

Citation

Mika Shimamura, Mami Nakahara, Tomomi Kurashige, Kazuaki Yasui, Masahiro Nakashima, Yuji Nagayama. Disruption of transforming growth factor-β signaling in thyroid follicular epithelial cells or intrathyroidal fibroblasts does not promote thyroid carcinogenesis. Endocrine journal. 2014;61(3):297-302