Actions of epidermal growth factor and its receptor in the thyroid

Nilsson, Mikael

doi:10.1016/1043-2760(95)00080-2

Cited by 16 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, EGF is inferred a role in both hyperplastic and neoplastic growth (Nilsson, 1995) and TGF-β is proven to be a key regulator in, for example, the development of thyroid fibrosis (Contempre et al, 1996). Thus, normal and highly differentiated epithelial cells in primary culture are here shown to be able to convert to a mesenchymallike phenotype provided the appropriate stimulus.…”

Section: Journal Of Cell Science 115 (22)mentioning

confidence: 90%

Transforming growth factor-β and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes

Grände

Franzén

Karlsson

et al. 2002

Journal of Cell Science

Self Cite

205

145

View full text Add to dashboard Cite

Enhancement of tumor cell growth and invasiveness by transforming growth factor-β (TGF-β) requires constitutive activation of the ras/MAPK pathway. Here we have investigated how MEK activation by epidermal growth factor (EGF) influences the response of fully differentiated and growth-arrested pig thyroid epithelial cells in primary culture to TGF-β1. The epithelial tightness was maintained after single stimulation with EGF or TGF-β1 (both 10 ng/ml) for 48 hours. In contrast, co-stimulation abolished the transepithelial resistance and increased the paracellular flux of [3H]inulin within 24 hours. Reduced levels of the tight junction proteins claudin-1 and occludin accompanied the loss of barrier function. N-cadherin, expressed only in few cells of untreated or single-stimulated cultures, was at the same time increased 30-fold and co-localised with E-cadherin at adherens junctions in all cells. After 48 hours of co-stimulation, both E- and N-cadherin were downregulated and the cells attained a fibroblast-like morphology and formed multilayers. TGF-β1 only partially inhibited EGF-induced Erk phosphorylation. The MEK inhibitor U0126 prevented residual Erk phosphorylation and abrogated the synergistic responses to TGF-β1 and EGF. The observations indicate that concomitant growth factor-induced MEK activation is necessary for TGF-β1 to convert normal thyroid epithelial cells to a mesenchymal phenotype.

show abstract

Section: Journal Of Cell Science 115 (22)mentioning

confidence: 90%

Transforming growth factor-β and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes

Grände

Franzén

Karlsson

et al. 2002

Journal of Cell Science

Self Cite

205

145

View full text Add to dashboard Cite

show abstract

“…EGF is synthesized within the thyroid gland and induces proliferation in thyroid cells from a wide range of species at the expense of dedifferentiation and loss of specialized thyroid-specific function (46). Over expression of EGF and GF-receptor in RNAS were detected in dyshormonogenetic goiters that were under constant and prolonged endogenous TSH stimulation (47).…”

Section: Increased Thyroid Cell Egf-induced Proliferationmentioning

confidence: 99%

Relevance of iodine intake as a reputed predisposing factor for thyroid cancer

Knobel

Medeiros‐Neto

2007

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

Iodine is a trace element that is essential for the synthesis of thyroid hormone. Both chronic iodine deficiency and iodine excess have been associated with hypertrophy and hyperplasia of follicular cells, attributed to excessive secretion of TSH. This may be associated to thyroid cancer risk, particularly in women. Experimental studies have documented thyroid cancer induction by elevation of endogenous TSH, although in a small number of animals. Iodine deficiency associated with carcinogenic agents and chemical mutagens will result in a higher incidence of thyroid malignancy. Inadequate low iodine intake will result in increased TSH stimulation, increased thyroid cell responsiveness to TSH, increased thyroid cell EGF-induced proliferation, decreased TGFβ 1 production and increased angiogenesis, all phenomena related to promotion of tumor growth. Epidemiological studies associating iodine intake and thyroid cancer led to controversial and conflicting results. There is no doubt that introduction of universal iodine prophylaxis in population previously in chronic iodine-deficiency leads to a changing pattern of more prevalent papillary thyroid cancer and declining of follicular thyroid cancer. Also anaplastic thyroid cancer is practically not seen after years of iodine supplementation. Iodine excess has also been indicated as a possible nutritional factor in the prevalence of differentiated thyroid cancer in Iceland, Hawaii and, more recently, in China. In conclusion: available evidence from animal experiments, epidemiological studies and iodine prophylaxis has demonstrated a shift towards a rise in papillary carcinoma, but no clear relationship between overall thyroid cancer incidence and iodine intake.

show abstract

“…Changes in the EGFR expression by TH have been documented in vivo as well as in cultured cells of some species (Fisher & Lakshmanan 1990, Nilsson 1995 but not in thyroid cells. Variations in EGFR levels seem not to be involved in the proliferative effect of T 3 in our system since no changes in the EGFR expression were detected after T 3 exposure.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, in FRTL-5 cells it was observed that T 3 attenuated the expression of the sodium iodide symporter (Spitzweg et al 1999). By coincidence, EGF is a strong inhibitor of thyroid function in several species, as well as a potent proliferative agent (Fisher & Lakshmanan 1990, Nilsson 1995. Therefore, the possibility that the inhibitory effect of T 3 on thyroid function could be mediated by an autocrine action of EGF as we propose for the T 3 -proliferative effect should be addressed.…”

Section: Discussionmentioning

confidence: 99%

“…Several growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factor I (IGF-I) and others, whose actions are mediated by tyrosine kinase (TK) receptors, have been shown to be important for thyroid cell proliferation in all the model systems tested so far (Dumont et al 1992, Bidey et al 1999. Some of these factors are reported to be involved in thyroid folliculogenesis and goitrogenesis (Nilsson 1995, Roger et al 1997, Bidey et al 1999. Moreover, a thyroid hormone-dependent increase in the levels of immunoreactive EGF and EGF-messenger ribonucleic acid (mRNA) in the mouse thyroid gland has been reported, suggesting that T 3 R could modulate the thyroid function through EGF (Osawa et al 1991, Sheflin et al 1993.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tri-iodothyronine induces proliferation in cultured bovine thyroid cells: evidence for the involvement of epidermal growth factor-associated tyrosine kinase activity

Fulvio

Coleoni²,

Pellizas³

et al. 2000

Journal of Endocrinology

View full text Add to dashboard Cite

The effects of the tri-iodothyronine (T 3 ) secreted by thyroid cells on the growth of the thyrocyte are poorly known. In this study we analyzed the effects of T 3 on the proliferation of bovine thyroid follicles in primary culture previously depleted of endogenous T 3 . Cellular deoxiribonucleic acid (DNA) synthesis, determined by [ 3 H]thymidine incorporation, was stimulated by T 3 (0·1-5·0 nM) for 24 h in a concentration-dependent fashion with a maximal effect at 1·0 nM T 3 (P<0·01). This T 3 action was time-dependent when assayed from 12 to 72 h. The induction of mitogenic activity was corroborated by the increase in proliferating cell nuclear antigen (PCNA) measured by Western blot analysis. PCNA increased after treatment with T 3 (0·1-5·0 nM) in a concentrationdependent manner. Since T 3 modifies the activity of growth factors whose actions are mainly mediated by tyrosine kinase (TK) activation in diverse cellular types, we assayed the effects of genistein, a general TK inhibitor, and tyrphostin A25, a specific epidermal growth factor (EGF)-receptor (EGFR)-dependent TK activity inhibitor, on the proliferative effects of T 3 . The T 3 -induced [ 3 H]thymidine incorporation was inhibited by both agents in a concentration-dependent manner. A significant increase in the total TK activity measured in cellular protein extracts was induced by 0·5 and 1·0 nM T 3 (P<0·001). Tyrosine phosphorylation of the EGFR was also stimulated by T 3 (P<0·001) with no change in the EGFR expression as determined by Western blot analysis. Both, the T 3 -stimulated [3 H]thymidine incorporation and the TK activity were inhibited by a anti-mouse EGF antibody. These results lead us to propose that T 3 could operate as a proliferative agent in bovine thyroid cells through a mechanism involving an autocrine/paracrine EGF/EGFR-dependent regulation.

show abstract

Actions of epidermal growth factor and its receptor in the thyroid

Cited by 16 publications

References 44 publications

Transforming growth factor-β and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes

Transforming growth factor-β and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes

Relevance of iodine intake as a reputed predisposing factor for thyroid cancer

Tri-iodothyronine induces proliferation in cultured bovine thyroid cells: evidence for the involvement of epidermal growth factor-associated tyrosine kinase activity

Contact Info

Product

Resources

About