EGF and TGF-1 Effects on Thyroid Function

Abstract

Normal epithelial thyroid cells in culture are inhibited by TGF-β1. Instead, transformed thyroid cell lines are frequently resistant to its growth inhibitory effect. Loss of TGF-β responsiveness could be due to a reduced expression of TGF-β receptors, as shown in transformed rat thyroid cell lines and in human thyroid tumors, or to alterations of other genes controlling TGF-β signal transduction pathway. However, in thyroid neoplasia, a complex pattern of alterations occurring during transformation and progression has been identified. Functionally, TGF-β1 acts as a tumor suppressor in the early stage of transformation or as a tumor promoter in advanced cancer. This peculiar pleiotropic behaviour of TGF-β may result from cross-talk with signalling pathways mediated by other growth factors, among which EGF-like ligands play an important role. This paper reports evidences on TGF-β1 and EGF systems in thyroid tumors and on the cross-talk between these growth factors in thyroid cancer.

Transcriptional activity of TGFβ1 and its receptors genes in thyroid gland

“…These tumours were associated with increased invasiveness and metastasis with an increased propensity towards epithelial to mesenchymal transition [20,21,22]. In PTC cell lines and animal models, TGFb signalling has been shown to regulate cellular epithelial to mesenchymal transition [19,20,22,25]. In thyroid PTC …”

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

“…It has long been well known that TGF-β suppresses growth of normal thyroid follicular epithelial cells [11,12]. However, the effect of TGF-β on thyroid cancer cell behavior is controversial.…”

“…In the thyroids, as for other tissues, expression of TGF-β ligands and their receptors and their effects on growth of normal cells and established cancer cells have previously been studied [11,12], but yet the effect of TGF-β signaling on early thyroid carcinogenesis remained to be determined. In this current study, therefore, Tgfbr2 floxE2/floxE2 mice were crossed with FSP1-Cre or thyroid peroxidase (TPO)-Cre mice to study the significance of TGF-β signaling in thyroid follicular epithelial cells and surrounding fibroblasts for thyroid early carcinogenesis.…”

Dysregulation of clathrin promotes thyroid cell growth and contributes to multinodular goiter pathogenesis

“…In particular, the activated form of the protein, pSTAT3, is significantly up-regulated in PTC with high metastatic potential [11]. All these evidence suggest that an optimal level EGF-STAT3 signaling must be achieved and cumulative alterations in this signaling pathway may lead to the stepwise transition towards malignancy, including gaining resistance to growth inhibition and ability to proliferate independently on growth factors and to replicate infinitely [12].…”