Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors

Dumont, Jacques Emile; Lamy, Françoise; Roger, Pierre P.; Maenhaut, Carine

doi:10.1152/physrev.1992.72.3.667

Cited by 526 publications

(373 citation statements)

References 106 publications

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“…In this physiologically relevant system [17,18], cAMP positively controls a late G1 R point [19]. The induction of DNA synthesis in the presence of insulin by the general adenylyl cyclase activator forskolin requires its continuous presence for at least 16 h. In the presence of forskolin dog thyrocytes progress toward S phase, but if this factor is withdrawn for as little as 2 h before cells reach the commitment point, they rapidly regress to an earlier part of G1, from which they can be rescued by forskolin readdition [19].…”

Section: Introductionmentioning

confidence: 99%

Nature of the Critical Labile Event That Controls RB Phosphorylation in the Cyclic AMP-Dependent Cell Cycle of Thyrocytes in Primary Culture

Roger

Demartin

Dumont

1999

Experimental Cell Research

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This study addresses the nature of the critical labile event that couples at restriction point mitogenic cascades with the autonomous part of the cell cycle. In primary cultures of dog thyroid epithelial cells, kinetic experiments indicate that a labile cAMP-dependent event positively controls a late G1 commitment to DNA replication and RB phosphorylation. As previously shown in this system, the cAMP-dependent mitogenic pathway differs from the most generally envisaged growth factor cascades as it stimulates the accumulation of p27 kip1 but not of cyclins D. Nevertheless, cyclin D3 and CDK4 activity are essential in the cAMP-dependent mitogenesis, and cAMP unmasks the DCS-22 epitope of cyclin D3 and induces the nuclear translocations and assembly of cyclin D3 and CDK4 in a complex that also contains p27 kip1 . Unexpectedly, the washing out of forskolin rapidly arrested S phase entry and the accumulation of hyperphosphorylated RB, but did not reverse any of the above events associated with cyclin D3-CDK4 activation. This implies that even after induction of stable nuclear cyclin D3-CDK4 complexes, dog thyrocytes still depend on cAMP for RB phosphorylation and commitment to DNA synthesis, which suggests that a key labile event responsible for a last control of restriction point passage remains to be uncovered, in the cAMP-dependent cell cycle of dog thyrocytes and possibly other systems.

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Section: Introductionmentioning

confidence: 99%

Nature of the Critical Labile Event That Controls RB Phosphorylation in the Cyclic AMP-Dependent Cell Cycle of Thyrocytes in Primary Culture

Roger

Demartin

Dumont

1999

Experimental Cell Research

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“…17 Embryonic remnants have been identified in adult thyroid tissue as small clusters, the solid cell nests (SCNs), which could represent a potential niche of thyroid SCs defined by the expression of tumour protein 63 (p63, Table 1). 30 SNC is composed of centrally located undifferentiated p63 − cells, and surrounded by p63 + cells with a basal/SC phenotype clustered or structured within a single layer.…”

Section: Normal Thyroid Stem Cellsmentioning

confidence: 99%

“…51,52 Considering the SCN as a source for both follicular and C cells, the presence of three cell types has been hypothesised: (i) progenitors of follicular cells, arisen from the base of the foregut (endodermal origin); (ii) progenitors of C cells, which originate from ultimobranchial bodies (neural crest origin); and (iii) and the follicular and C bipotential progenitor cells. 8 In 1992, Dumont et al 17 first hypothesised the existence of ASCs within the mature thyroid gland. Thomas et al isolated a population of ASCs from the goitre, characterised by the co-expression of the octamer-binding protein 4 (Oct-4) stem pluripotent marker, the transcription factor GATA-4 and hepatocyte nuclear factor 4-α (HNF-4-α) endodermal markers and Pax-8.…”

Section: Normal Thyroid Stem Cellsmentioning

confidence: 99%

“…13,14 However, this model is not in accordance with the rare occurrence of RET/PTC and PAX8/PPARG rearrangements in ATC 15 and the low turnover rate of thyroid follicular cells (about five renewals per lifetime) that reduces the possibility of accumulating the mutations needed for transformation. 8,[16][17][18] The existence of several differentiation degrees has led to the assumption that TC cells are derived from remnants of fetal thyroid cells, such as stem cells (SCs) or precursors, rather than mature follicular cells. 9,19,20 According to this fetal cell carcinogenesis model supported by gene expression profiling data, ATC arises from fetal thyroid SCs, marked by the onco-fetal fibronectin expression and lack of differentiation markers.…”

Section: Introductionmentioning

confidence: 99%

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Normal vs cancer thyroid stem cells: the road to transformation

et al. 2015

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Recent investigations in thyroid carcinogenesis have led to the isolation and characterisation of a subpopulation of stem-like cells, responsible for tumour initiation, progression and metastasis. Nevertheless, the cellular origin of thyroid cancer stem cells (SCs) remains unknown and it is still necessary to define the process and the target population that sustain malignant transformation of tissue-resident SCs or the reprogramming of a more differentiated cell. Here, we will critically discuss new insights into thyroid SCs as a potential source of cancer formation in light of the available information on the oncogenic role of genetic modifications that occur during thyroid cancer development. Understanding the fine mechanisms that regulate tumour transformation may provide new ground for clinical intervention in terms of prevention, diagnosis and therapy.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.138

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“…The Tg-A 2a R transgene promotes in mice, as the cyclic AMP (cAMP) cascade in dog thyroid epithelial cells in primary culture, both cell proliferation and function (Roger et al, 1982;Roger and Dumont, 1984;Dumont et al, 1992), resulting in the appearance of a di erentiated goiter and severe hyperthyroidism (Ledent et al, 1992). This model, as the model of mice expressing in the thyroid a G sa mutant (Michiels et al, 1994), mimics the human autonomous hyperfunctional adenomas and non-autoimmune familial hyperthyroidism due to mutations activating the cAMP pathway, such as the constitutive activation of the thyrotropin receptor , or of the G sa protein (Lyons et al, 1990;Suarez et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Differential patterns of cell cycle regulatory proteins expression in transgenic models of thyroid tumours

et al. 1998

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Cell cycle proteins regulate the transitions from G1 to S and G2 to M phases. In higher eukaryotes, their function is controlled by intracellular cascades regulated by extracellular growth factors. We have studied in previously described transgenic mouse models for thyroid proliferative diseases the expression of the key proteins regulating the cell cycle by Western blotting and immunohistochemistry, and have correlated the observations with the known actions of the transgenes on the signal transduction cascades. In the adenosine A 2a receptor model, the cyclic AMP pathway, upstream of the Rb family cell division block, is constitutively activated. In the model expressing HPV 16 E7 protein, the Rb-like proteins are inhibited. Cyclin-dependent kinases cdk4, cdk2 and cdc2, and the associated cyclins D, E and A have been studied. Cyclin D3 appears as the major cyclin D subtype expressed in mouse thyroid epithelial cells in normal and transgenic mice. In the adenosine A 2a R model, all cell cycle proteins tested were accumulated. In the E7 model, all cell cycle proteins except for D-type cyclins and cdk4 were also accumulated. A similar pattern was observed in thyroids coexpressing both transgenes, suggesting a dominant e ect of E7 over the consequences of the cAMP cascade activation. The cyclin-dependent kinase inhibitors p21 cip1/waf1 and p27 kip1 were not downregulated in these proliferating thyroids which suggest other roles than the inhibition of the cell cycle progression.

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Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors

Cited by 526 publications

References 106 publications

Nature of the Critical Labile Event That Controls RB Phosphorylation in the Cyclic AMP-Dependent Cell Cycle of Thyrocytes in Primary Culture

Nature of the Critical Labile Event That Controls RB Phosphorylation in the Cyclic AMP-Dependent Cell Cycle of Thyrocytes in Primary Culture

Normal vs cancer thyroid stem cells: the road to transformation

Differential patterns of cell cycle regulatory proteins expression in transgenic models of thyroid tumours

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