Structure, Function and Expression of the Human Calcitonin/α-CGRP Gene

Marshall, Ian; Al-Kazwini, Susan J.; Holman, Jenny J.; Broad, Peter; Edbrooke, Mark R.; Craig, Roger K.

doi:10.1007/978-1-4684-5131-3_1

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…The role of CGRP as a vasodilatatory agent in mammals, including man, is also now well documented (see Gennari & Fischer, 1985;Marshall et al, 1986). Since we cannot detect the CGRP product of the calcitonin/a-CGRP gene in turnour tissue, either at the peptide (immunocytochemistry) or mRNA (in-situ hybridization) levels, we conclude that the elevated levels of plasma CGRP in the non-small cell lung carcinomas most probably reflect a consequence of the tumours on cardiovascular haemodynamics.…”

Section: Discussionmentioning

confidence: 99%

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Elevated Serum Levels of Calcitonin Gene‐related Peptide (Cgrp) but No Evidence for CGRP Gene Expression in Non‐small Cell Lung Carcinomas

Schifter

Johannsen

Aagaard

et al. 1989

Clinical Endocrinology

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Calcitonin gene-related peptide (CGRP) is a hormone formed by alternative post-transcriptional processing of the calcitonin gene. It is a neuropeptide localized to discrete regions of the central nervous system (CNS) and in nerve fibres associated with blood vessels. It is also expressed in medullary carcinomas of the thyroid and lung carcinoma cell lines. The latter finding suggests a possible value for CGRP as tumour marker in lung carcinomas. In this investigation of 22 patients undergoing operation for lung tumours, pre and post-operative levels of serum CGRP were measured. Preoperative as well as postoperative serum CGRP levels were significantly elevated when compared to age-matched normals. However, no evidence could be found for CGRP gene expression in tumour tissue from the same patients as judged by immunocytochemistry or in-situ hybridization using CGRP cRNA probes. CGRP has been localized to nerve fibres in relation to pulmonary blood vessels and has been shown to be a potent vasodilator. These findings, and the absence of evidence for synthesis in tumours, as opposed to cell lines derived from lung carcinomas, suggests that the lack of post-operative normalization of serum CGRP concentrations may be related to physiological changes in cardiovascular haemodynamics following surgery. Elevated pre-operative serum CGRP levels may also reflect a consequence of the lung carcinoma leading to increased release of CGRP from sites in the vasculature yet to be determined, but does not indicate synthesis de novo and secretion of CGRP by the tumours.

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Section: Discussionmentioning

confidence: 99%

“…A second gene encoding a similar peptide (P-CGRP) has also been isolated (Steenbergh et al, 1985). Several investigations have shown that CGRP has profound effects on the cardiovascular system in many species including man (Brain et al, 1985;Gennari & Fischer, 1985;Marshall et al, 1986).…”

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Elevated Serum Levels of Calcitonin Gene‐related Peptide (Cgrp) but No Evidence for CGRP Gene Expression in Non‐small Cell Lung Carcinomas

Schifter

Johannsen

Aagaard

et al. 1989

Clinical Endocrinology

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“…CT is found mainly in thyroid C-cells (Austin & Heath, 1981, review), while CGRP is localized mainly in the central and peripheral nervous system in nerve fibres with relation to the cardiovascular system (Mulderry et al, 1985;Zaidi et al, 1985Zaidi et al, , 1986Uddman et al, 1986). CGRP is a neurotransmitter with a pronounced vasodilatory effect (Brain et al, 1985;Gennari & Fischer, 1985;Girgis et al, 1985;Marshall et al, 1986), and circulates in the blood (Girgis et al, 1985;Schifter, 1991). The main source of circulating CGRP seems to be nerve terminals with relation to the vasculature (Zaidi et al, 1985 indicating a role in cardiovascular regulation (Gennari & Fischer, 1985;Marshall et al, 1986;Craig et al, 1986;Struthers et al, 1986).…”

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confidence: 99%

“…CGRP is a neurotransmitter with a pronounced vasodilatory effect (Brain et al, 1985;Gennari & Fischer, 1985;Girgis et al, 1985;Marshall et al, 1986), and circulates in the blood (Girgis et al, 1985;Schifter, 1991). The main source of circulating CGRP seems to be nerve terminals with relation to the vasculature (Zaidi et al, 1985 indicating a role in cardiovascular regulation (Gennari & Fischer, 1985;Marshall et al, 1986;Craig et al, 1986;Struthers et al, 1986).…”

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Calcitonin gene‐related peptide in small cell lung carcinomas

Schifter

Johannsen

Bunker

et al. 1993

Clinical Endocrinology

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We found that patients with small cell lung carcinomas had elevated concentration of serum calcitonin gene-related peptide but only 27% had values above the upper normal range. Serum CGRP is therefore of limited value as a tumour marker. Intact CGRP can be extracted from tumour tissue, but in-situ hybridization and immunohistochemistry showed positive reactions in only a few of the tumours investigated. The elevated serum CGRP levels are therefore likely to be largely of extratumoral origin.

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