Expression of the Second Calcitonin/Calcitonin Gene-Related Peptide Gene in Ewing Sarcoma Cell Lines*

Höppener, Jo W.M.; Steenbergh, P. H.; Slebos, Robert J. C.; Visser, Allerdien; Lips, Cornelis J.M.; Jansz, H.S.; Bechet, Jean Marie; Lenoir, G.; Born, Walter; Haller-Brem, Susanne; Petermann, Josef B.; Fischer, Jan A.

doi:10.1210/jcem-64-4-809

Cited by 37 publications

(12 citation statements)

References 38 publications

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“…The primary RNA transcript for the CALC I gene is differentially processed in a cell-specific manner to include exon 4 in the thyroidal C-cells and exclude this exon in neuronal cells. However, mRNAs containing the CALC II exon 4 have never been observed in tissues or cell lines expressing this gene (5,6). The CALC Ill gene lacks an exon 4 region.…”

Section: Introductionmentioning

confidence: 99%

Identification of exon sequences and an exon binding protein involved in alternative RNA splicing of calcitonin/CGRP

Cote¹,

Stolow²,

Peleg³

et al. 1992

Nucl Acids Res

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Transcripts derived from the 6 exon CALC I gene are differentially processed in a tissue-specific fashion to include or exclude a calcitonin-specific exon 4. All cell types which transcribe a second calcitonin/CGRP gene, CALC II, exclude exon 4. Substitution of the first 30 nucleotides of CALC I exon 4 with analogous CALC II sequence was sufficient to prevent recognition of exon 4 in in vitro or in vivo RNA splicing systems. UV crosslinking detected a approximately 66 kDa RNA-binding protein in HeLa nuclear extract which interacted with CALC I proximal exon sequence, but not CALC II or mutant sequences. UV crosslinking of this protein was inhibited by addition of nuclear extract from a cell type which normally causes exclusion of exon 4. These results identify an important regulatory element within exon 4 and support a model in which calcitonin production requires protein interaction with this sequence to facilitate exon recognition.

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Section: Introductionmentioning

confidence: 99%

Identification of exon sequences and an exon binding protein involved in alternative RNA splicing of calcitonin/CGRP

Cote¹,

Stolow²,

Peleg³

et al. 1992

Nucl Acids Res

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“…Recently there has been evidence that Ewing cells share a number of similarities with tumors of neuroectodermal origin [69][70][71]. As in neuronal tumor cell lines, Ewing cells contain nerve growth factor receptors and are undif ferentiated small round-shaped cells [70], Although the second calcitonin gene peptide is expressed in these cells [72], no VP or OT mRNA expression was detected.…”

Section: Non-neuroendocrine Tumor Cell Linesmentioning

confidence: 99%

Survey of Neuropeptide Gene Expression in Tumor Cell Lines

et al. 1992

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The presence of 3 different neuropeptide mRNAs with a strict cell-specific expression in vivo was investigated in 13 tumor cell lines from neuroendocrine and in 23 tumor cell lines from non-neuroendocrine origin. Northern blots showed no expression of mRNA for vasopressin (VP) in the 36 tested cell lines. Very low oxytocin (OT) mRNA hybridization signals were detected in the rat pituitary tumor cell line GH4C2 and the rat pancreas tumor cell line RIN5. Both the rat pituitary tumor cell line AtT-20 and the human myeloid leukemia cell line K562, contained proopiomelanocortin (POMC) mRNA. The low incidence of VP, OT and POMC gene expression in the tested tumor cell lines was not influenced by treatments inducing differentiation. In contrast, the cholecystokinin (CCK) gene which is widely present in nervous and endocrine systems was abundantly expressed in the human primitive neuroepithelioma cell line SK-N-MC and its clonal derivative SK-N-MC-IX-C. The results indicate that the expression of neuropeptide genes is very rare in tumor cell lines. The lack of expression in undifferentiated cells agrees with the appearance of expression after day 13 of the embryogenesis when maturation of neurons begins.

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“…In man, the two genes are located on the same chromosome 11 and may have arisen by gene duplication (31). The relative expression of human CGRP I and II at the level of mRNA and mature peptides varies in different tissues (6,15,28, 34,35). CGRP exerts profound effects on the cardiovascular system of man and experimental animals, which include vasodilatation, positive chronotropic and ionotropic actions on the heart, and stimulation of plasma renin activity (5, 9-11, 20, 32).…”

Section: Aldosteronementioning

confidence: 99%

Distinct hemodynamic and gastric effects of human CGRP I and II in man

et al. 1991

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Distinct hemodynamic and gastric effects of human CGRP I and H in man. PEPTIDES 12(6) [1347][1348][1349][1350][1351] 1991.--The human calcitonin gene-related peptides I and II (or ct and 13) (CGRP I and II) are encoded by two different genes, but they have 34 of the 37 amino acid residues in common. Human CGRP I more potently stimulated blood flow through the skin and carotid artery (p<0.01), and the heart rate (p<0.05), and plasma renin activity and aldosterone secretion than human CGRP H (p<0.02). Inhibition of pentagastrin-stimulated gastric acid output, on the other hand, was only obtained with CGRP II. The separate effects of human CGRP I and I1 on the cardiovascular and gastric systems are presumably mediated by different receptors or receptor pathways recognized by the two closely related neuropeptides. AldosteroneCalcitonin gene-related peptide Gastric acid secretion Renin activity Vasodilatation HUMAN and rat calcitonin gene-related peptides I and II (or ct and 13) (CGRP I and II) differ in only 3 and 1 of the 37 amino acid residues, respectively (1,31). They are products of two separate genes. In man, the two genes are located on the same chromosome 11 and may have arisen by gene duplication (31). The relative expression of human CGRP I and II at the level of mRNA and mature peptides varies in different tissues (6,15,28, 34,35). CGRP exerts profound effects on the cardiovascular system of man and experimental animals, which include vasodilatation, positive chronotropic and ionotropic actions on the heart, and stimulation of plasma renin activity (5, 9-11, 20, 32). The latter effect represents a counterregulatory mechanism to the hypotension evoked by CGRP, but CGRP also directly stimulated the release of renin from juxtaglomerular cells (20). CGRP, moreover, inhibits gastric acid secretion with unchanged mucosal blood flow (19,22,23,33). We have reported earlier that human CGRP II, unlike CGRP I, inhibits pentagastrin-stimulated acid output (3).To address other potentially different biological targets of human CGRP I and II, we have now compared the cardiovascular effects of the two CGRPs, and have reexamined the inhibition of gastric acid output. The results provide evidence that human CGRP I more potently stimulates blood flow in the skin and the common carotid artery, and plasma renin activity and aldosterone levels than CGRP II, but does not suppress gastric acid secretion.1Requests for reprints should be addressed to Dr. J. A. Fischer, Klinik METHOD PeptidesSynthetic human CGRP I and II (or a and 13) were purchased from Peninsula Laboratories (Belmont, CA). Over 95% of the immunoreactive material eluted as a single peak on reversedphase HPLC (28). The CGRP was dissolved in 0.15 M NaC1 containing 0.1% human serum albumin, and vials containing 6.6 nmol/ml were prepared under aseptic conditions by the University of Basel Hospital Pharmacy and were stored at -20°C. The concentration of CGRP peptides obtained by weighing and by radioimmunoassay was within 10% of the predicted values.Pentagastrin (Pep...

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Expression of the Second Calcitonin/Calcitonin Gene-Related Peptide Gene in Ewing Sarcoma Cell Lines*

Cited by 37 publications

References 38 publications

Identification of exon sequences and an exon binding protein involved in alternative RNA splicing of calcitonin/CGRP

Identification of exon sequences and an exon binding protein involved in alternative RNA splicing of calcitonin/CGRP

Survey of Neuropeptide Gene Expression in Tumor Cell Lines

Distinct hemodynamic and gastric effects of human CGRP I and II in man

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