Calcitonin gene expression in normal human liver

Bracq, S.; Machairas, M; Clément, Bruno; Pidoux, E.; Andreoletti, Marion; Moukhtar, M.S.; Jullienne, A.

doi:10.1016/0014-5793(93)80288-6

Cited by 25 publications

(12 citation statements)

References 13 publications

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“…In non-septic human tissue, mRNA of PCT was detected in the liver [28], but also in other organs such as the lung, kidney or testis [29]. During sepsis, mRNA of PCT and PCT as a protein have been detected in various types of leukocytes [26], liver tissue and other cell types [30].…”

Section: Discussionmentioning

confidence: 97%

Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications

et al. 2002

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Elevated PCT, but not CRP, correlates with evidence of systemic inflammation and other complications early postoperatively after cardiac surgery. Although the PCT levels do not rise as quickly as the criteria of the systemic inflammatory response syndrome appear, they do reflect systemic inflammation. Early identification and quantification of a systemic inflammatory response may help reduce postoperative complications.

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Section: Discussionmentioning

confidence: 97%

Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications

et al. 2002

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“…Foxa2 was originally believed to be primarily involved in hepatic gene functions, and indeed low levels of CT mRNA have been reported in the liver (39). However, it is now clear that Foxa2 plays important roles outside the liver, including the control of neuronal and neuroendocrine genes.…”

Section: Foxa2 and Usf Activation Of Ct/cgrpmentioning

confidence: 99%

Regulation of the Cell-specific Calcitonin/Calcitonin Gene-related Peptide Enhancer by USF and the Foxa2 Forkhead Protein

Viney

Schmidt

Gierasch

et al. 2004

Journal of Biological Chemistry

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An 18-bp enhancer controls cell-specific expression of the calcitonin/calcitonin gene-related peptide gene. The enhancer is bound by a heterodimer of the bHLH-Zip protein USF-1 and -2 and a cell-specific factor from thyroid C cell lines. In this report we have identified the cell-specific factor as the forkhead protein Foxa2 (previously HNF-3␤). Binding of Foxa2 to the 18-bp enhancer was demonstrated using electrophoretic mobility shift assays. The cell-specific DNA-protein complex was selectively competed by a series of Foxa2 DNA binding sites, and the addition of Foxa2 antiserum supershifted the complex. Likewise, a complex similar to that seen with extracts from thyroid C cell lines was generated using an extract from heterologous cells expressing recombinant The calcitonin/calcitonin gene-related peptide (CT 1 /CGRP) gene expresses the hormone CT in thyroid C cells and the neuropeptide CGRP in neurons. CT is a therapeutically useful modulator of bone metabolism and calcium homeostasis (1), but it may also play additional roles based on the recent unexpected finding of increased bone mass in CT/CGRP and CT receptor knock-out mice (2-4). CGRP is an alternative splicing product from the CT/CGRP gene (5) that is now appreciated to be a member of a gene family of multifunctional neuropeptides that act on related receptors (6 -8). Most notably, CGRP is the most potent peptide dilator known (9, 10), and abnormal levels of CGRP have been implicated in neurovascular and cardiovascular disorders (7,(11)(12)(13). Importantly, CGRP antagonists have recently been reported to be an effective treatment for migraine (14).Regulation of CGRP expression in response to extracellular stimuli is controlled exclusively at the transcriptional level. Studies on both the human and rat CT/CGRP gene have identified a cell-specific enhancer containing helix-loop-helix (HLH) motifs ϳ1 kb upstream of the transcription start site (15-19). We have shown that an 18-bp element with a single HLH site and a flanking octamer-like motif is both sufficient and necessary for cell-specific enhancer activity (18, 19). Using nuclear extracts prepared from the neuronal-like CA77 thyroid C cell line, bHLH-Zip proteins USF-1 and -2 were shown to bind the enhancer in vitro (19). Although Oct1 can bind the A/T-rich half of the flanking site, Oct1 cannot transactivate the enhancer (18). Instead, a cell-specific protein referred to as OB2 was shown to bind an adjacent 8-bp site that partially overlaps the HLH site (19). OB2 was identified as an ϳ68-kDa protein by UV-cross-linking and is present in human and rat thyroid C cell lines but not in cell lines that do not express the CT/CGRP gene (19).In this study have shown that OB2 is the forkhead protein Foxa2, formerly called HNF-3␤. We demonstrate that Foxa2 is able to bind and activate the CT/CGRP enhancer in heterologous cells. Importantly, this transactivation requires the adjacent HLH site and is increased upon co-expression of USF. The combinatorial role of Foxa2 and USF was further demonstrated by short...

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“…Calcitonin and its receptor are expressed by both normal and malignant tissues such as liver (27) and prostate (28). In the case of prostate, CT seems to have a proliferative action (29), thus suggesting the possibility of an autocrine/paracrine function.…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Receptor mRNA is Expressed in Human Medullary Thyroid Carcinoma

Frendo

Delage-Mourroux²,

Cohen³

et al. 1998

Thyroid

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We recently reported the presence of a truncated form (h-CTR2) of the human calcitonin receptor (CTR) in TT cells, a cell line derived from medullary thyroid carcinoma (MTC). This form (h-CTR2), characterized by the absence of 16 amino acids in the first intracellular domain, was also detected in two cases of MTC. In the present study we determined the expression of CTR mRNA in a larger sample, representative of the different clinical forms of MTC, and in normal thyroid. h-CTR2 was expressed in all MTC specimens (both sporadic and familial) and in the normal thyroid samples. The expression of the receptor mRNA was higher in MTC compared with normal thyroid. Moreover, CT and CTR mRNA levels were modified significantly during proliferation. This result suggests that CT may be involved in proliferation of MTC via autocrine/paracrine regulation. Calcitonin secretion by MTC may play a role in the development and spread of these tumors.

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Calcitonin gene expression in normal human liver

Cited by 25 publications

References 13 publications

Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications

Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications

Regulation of the Cell-specific Calcitonin/Calcitonin Gene-related Peptide Enhancer by USF and the Foxa2 Forkhead Protein

Calcitonin Receptor mRNA is Expressed in Human Medullary Thyroid Carcinoma

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