Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunoreactive calcitonin (CT) secreted by DMS 53, a cell line derived from human small cell carcinoma of the lung, consists almost entirely of molecular species larger than the mature hormone (Mr 3,420). Messenger RNA isolated from DMS 53 cells and nude mouse tumors was translated in wheat germ systems, and the products were precipitated with CT-specific antisera. Analyses of the translation products by electrophoresis on 15% polyacrylamide-sodium dodecyl sulfate gels indicated synthesis of a Mr 16,500 preprohormone that was reduced to Mr 14,500 by cotranslation with microsomal membranes. Immunoprecipitation of CT from media from pulse-labeled cultures revealed two major products (Mr 16,500 and Mr 14,500) and up to three minor secreted polypeptides (Mr 9,400, 8,400, and 6,800). Intracellular CT from cell homogenates appeared almost entirely as a single major product (Mr 14,500) and possibly 3-4 minor components (Mr 16,500; 9,200, 8,400, and 6,800). No glycosylated forms of CT were demonstrable by lectin binding methods or labeling attempts with tritiated sugars. The presence of multiple CT species in DMS 53 cells suggests significant post-translational processing of the larger precursor molecules and the accumulation and secretion by small cell carcinoma of the lung of several intermediate immunoreactive forms via a glycosylation-independent secretory pathway.
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PMID:Biosynthesis of procalcitonin in small cell carcinoma of the lung. 300 May 86

Generalized hypomethylation of the genome and of specific genes has been described in human tumors. We now report that in human lung cancers, especially in the most aggressive form, small cell lung carcinoma, and in lymphomas, the 5'-region of the calcitonin (CT) gene exhibits methylation of increased numbers of CCGG sites in comparison with normal adult tissues. These unusual methylation patterns are found much less frequently in other tumor types examined. In the spectrum of the four major types of lung cancer (small cell, adeno-, squamous, and large cell carcinomas), the frequency of occurrence of hypermethylation in the 5'-region of the CT gene parallels that for presence of the neuroendocrine related biochemistry which characterizes small cell lung carcinoma. In medullary thyroid carcinoma, a tumor which expresses high levels of CT gene mRNA, the 5'-region of the CT gene is hypomethylated. Our findings provide a potential new molecular marker for two important human cancers (lung cancer and lymphomas) and suggest that there is a close relationship between abnormal CT gene methylation and developmental events for these tumors.
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PMID:DNA methylation patterns of the calcitonin gene in human lung cancers and lymphomas. 300 2

Several recent studies have confirmed the endocrine nature of small cell carcinoma of the lung. In extra-pulmonary sites, small cell 'undifferentiated' carcinomas have classical morphological features similar to their pulmonary counterpart. We therefore investigated, using immunocytochemistry, the possibility that the non-pulmonary neoplasms may also be endocrine in nature. Sections of 29 small cell carcinomas from oesophagus, stomach, larynx, colon and urinary bladder were immunostained using antisera to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), cytokeratin, leucocyte common antigen and peptides including bombesin, the C-flanking peptide of human probombesin, adrenocorticotrophic hormone, neurotensin, calcitonin and pancreatic polypeptide. All the tumours showed immunoreactivity for at least one of the two general endocrine markers PGP 9.5 and NSE. Twenty-three of the 29 cases were immunoreactive for PGP 9.5, 27 for NSE. All were positive for cytokeratin and negative for leucocyte common antigen. Of the regulatory peptides, immunoreactivity was obtained with antisera to bombesin (one case), the C-flanking peptide of human pro-bombesin (14 cases), adrenocorticotrophic hormone (one case) and calcitonin (three cases). No PGP 9.5-, NSE- or peptide-like immunoreactivity was detected in 25 control tumours from similar sites, including lymphomas and poorly differentiated tumours. These results suggest that non-pulmonary small cell carcinoma has an endocrine character.
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PMID:Endocrine differentiation of extra-pulmonary small cell carcinoma demonstrated by immunohistochemistry using antibodies to PGP 9.5, neuron-specific enolase and the C-flanking peptide of human pro-bombesin. 302 89

Studies on the structure and expression of the rat and human calcitonin gene provide a remarkable example by which a combination of molecular, immunocytochemical and pharmacological techniques have led to the identification of a novel gene product, the calcitonin gene-related peptide, a peptide of unexpected tissue distribution and biological activity. Future studies at the molecular level will provide insight into post-transcriptional mechanisms by which a single gene can give rise to discrete mRNAs in a tissue-specific manner. The isolation and characterization of the CGRP receptor, and hence the site(s) and mechanism(s) of action of the CGRP family within the vasculature, will also add significantly to our understanding of molecular mechanisms involved in the modulation of cardiovascular function in man. Furthermore, the role and mechanism of action of the CGRP peptide family in the central and peripheral nervous systems remains to be elucidated. It is also apparent that measurement of circulating plasma levels of CGRP may be of diagnostic and prognostic value, providing information concerning the onset and progression of lung and thyroid carcinoma. Our analysis of the structure and expression of the calcitonin/alpha-CGRP gene also demonstrates, for the first time, the molecular basis of large calcitonin secretion by lung carcinoma cells. Whether the expression of this gene in lung carcinoma cell-lines can truly be described as 'ectopic' is however questionable, in the light of recent immunocytochemical evidence which demonstrates that the lung is a major source of CGRP producing cells in the rat (see Springall et al., 1984).
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PMID:Expression and function of the human calcitonin/alpha-CGRP gene in health and disease. 303 87

Cloning and nucleotide sequence analysis of the human calcitonin mRNA from the BEN lung carcinoma cell line, a cell line known to secrete high-Mr forms of calcitonin, showed no difference in the coding region at the nucleotide level compared with calcitonin mRNA isolated from medullary thyroid carcinoma which secretes calcitonin monomer. Therefore, the secretion of high-Mr forms of calcitonin reflects the absence or limited activity of proteolytic processing enzymes within the secretory pathway of this cell line. In all other respects, as judged by RNA blotting and S1 mapping, calcitonin/alpha-CGRP expression was identical to that found in medullary thyroid carcinoma, including the differential use of an alternative splice donor site within intron 1. The BEN cell line also produces low levels of alpha-CGRP mRNA and secretes CGRP antigenic determinants. Analysis of plasma CGRP levels in 12 patients with anaplastic lung carcinoma showed elevated levels in 11 of these, suggesting that CGRP may be an important diagnostic marker for this disease.
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PMID:Ectopic synthesis of high-Mr calcitonin by the BEN lung carcinoma cell line reflects aberrant proteolytic processing. 348 40

Expression of the calcitonin (CT)/calcitonin gene related peptide (CGRP) gene and the proopiomelanocortin (POMC) gene has been demonstrated by Northern blot hybridization analysis of RNA extracted from human medullary thyroid carcinoma (MTC), pheochromocytoma and lung carcinoma. CT mRNA in these tumors could not be distinguished in size from CT mRNA isolated from normal human thyroid tissue. CGRP mRNA (previously demonstrated in 12 out of 12 lung tumor cell lines investigated) could not be detected in 13 primary lung tumors or 10 metastases thereof. The length of POMC mRNA in MTCs (present in all 4 metastases investigated but not in 7 primary tumors) and pheochromocytomas is about 100 nucleotides more than pituitary POMC RNA. In lung tumors 2 POMC RNA species can be detected, one of the same size as in pituitary tissue and one about 100 nucleotides larger.
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PMID:Detection of mRNA encoding calcitonin, calcitonin gene related peptide and proopiomelanocortin in human tumors. 348 30

The serum immunoreactive calcitonin (ICT) concentration was estimated in 107 patients with lung cancer of various cell types, 46 normal subjects and 24 non-cancer patients with various pulmonary diseases. Eighty-one of the cancer patients had localized lung cancer and the rest 26 primary lung cancer with metastases to other organs. The ICT was found significantly increased in the lung cancer patients. The highest ICT values were found in patients with lung cancer and metastases to other organs, especially to the liver. In localized disease, patients with small-cell carcinoma of the lung showed the highest, while those with adenocarcinoma and squamous-cell type demonstrated the lowest ICT concentrations. In 46 patients with lung cancer, serial determinations of serum ICT levels showed significantly decreased calcitonin levels in the patients who responded well to therapy with cytostatics, X-rays or both after more than 2 months of therapy. Fluctuations of ICT levels were in agreement with the regression or progression of the disease.
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PMID:Calcitonin concentrations in lung cancer and non-malignant pulmonary diseases. 360 15

The association of hormonal syndrome and APUD (amine precursor uptake, decarboxylase) features with small cell carcinoma of the lung (SCC) has suggested that SCC has a separate cell origin from other major forms of lung cancer. Recently, however, both SCC and non-SCC lung cancers have been found to contain small polypeptide hormones and APUD enzymes. The present study quantitates, in 50 samples of human lung cancer tissue, relationships among the 4 major types of lung cancer and endocrine-related properties. Among 4 parameters measured (dopa decarboxylase, histaminase, beta-endorphin, and calcitonin), no single marker clearly separated SCC from non-SCC lung cancer. The high activity of dopa decarboxylase (the "D" in "APUD") best separated SCC from non-SCC, but significant overlap existed even for this critical APUD property. In fact, 2 adenocarcinomas had among the highest concentrations of dopa decarboxylase, histaminase, and calcitonin of any tumor tissue studied. The simultaneous appearance of high levels of 2 or more markers favored SCC. This was quantitated by deriving an index unit based upon the product of the values for the 4 markers in each lesion. This index separated all SCC from all non-SCC lung carcinomas, with the exception of the above 2 adenocarcinomas. Endocrine-related properties thus occur throughout the spectrum of human lung cancer. Biochemical differences between the major histopathological types are quantitative rather than qualitative and probably reflect the fact that the major forms of lung cancer represent a continuum of differentiation within a common cell lineage which includes both SCC and non-SCC lung tumors.
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PMID:Endocrine-related biochemistry in the spectrum of human lung carcinoma. 611 10

Three established cell lines derived from human small cell carcinoma of the lung, and known to produce significant amounts of peptide hormones were used to evaluate the regulation of hormone secretion by cholinergic agonists. In two of the cell lines (DMS 53, DMS 153) acetylcholine chloride, bethanechol chloride, and carbamylcholine at the concentrations of 10(-3)M to 10(-5)M stimulated secretion of bombesin and calcitonin as measured by RIA. The third cell line, DMS 406, was not significantly stimulated. Inhibition of induced stimulation by the cholinergic antagonist atropine, but not hexamethonium, indicated the presence of muscarinic rather than the nicotinic type of cholinergic receptors on the stimulatable cells. These receptors appear to mediate hormone secretion comparably to normal endocrine cells.
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PMID:Bombesin and calcitonin secretion by pulmonary carcinoma is modulated by cholinergic receptors. 613 24

Ectopic production of multiple peptide hormones is a frequent concomitant of neoplasia. An elderly man with metastatic small cell carcinoma of the lung presented with back pain, a right hilar mass, and was demonstrated to have markedly elevated serum calcitonin and amylase levels. Polyacrylamide gel electrophoresis revealed a striking elevation of a "salivary type" isoamylase. We report this case as an unusual association of production of both a peptide hormone and a nonhormonal peptide in a patient with a tumor of "neural crest" origin.
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PMID:Carcinoma of the lung with marked hyperamylasemia and elevated serum calcitonin. 617 7


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