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C J Lips

Publications and source records attributed to C J Lips.

At least 145 records · Page 8Linked to original sources

A second human calcitonin/CGRP gene.

The calcitonin (CT) gene is alternatively expressed in a tissue-specific fashion producing either the calcium regulatory hormone CT in the thyroid or the neuropeptide calcitonin gene related peptide (CGRP) in the brain. In medullary carcinoma of the thyroid both peptides are produced. We present here evidence for the existence in the human genome of a second CT gene, which is also expressed in human medullary thyroid carcinoma. This gene encodes a second human CGRP, differing from the known human CGRP in 3 of the 37 amino acids.

Amino Acid Sequence↗

Enolase isozymes in differentiated and undifferentiated medullary thyroid carcinomas.

Enolase isozyme composition was studied using both electrophoretic and chromatographic methods in rat medullary thyroid carcinomas (MTC), differing in their degree of differentiation. In well-differentiated rat tumors (DMTC), both the alpha- and gamma-subunits of enolase were expressed, resulting in alpha alpha, alpha gamma, and gamma gamma isozymes. The relatively high amount of alpha gamma and gamma gamma isozymes (neuron-specific enolase [NSE] ) was indicative of the presumed neuroectodermal origin of these tumors. In contrast, highly undifferentiated or anaplastic tumors (AMTC) were characterized by a decrease in expression of the gamma-subunit. Hence, the majority of enolase isozymes were alpha alpha dimers, with only a few percent alpha gamma hybrids remaining. These shifts from neuron-specific to non-neuronal isozymes in rat MTC were compared with human MTC and discussed with respect to neuronal differentiation and the clinical significance of NSE measurements in serum as a marker for amine precursor uptake and decarboxylation cell-derived neoplasms.

Animals↗

The second human calcitonin/CGRP gene is located on chromosome 11.

A second human calcitonin/calcitonin gene related peptide (hCT/CGRP) gene has been identified. This second hCT/CGRP gene has been shown to contain sequences highly homologous to exons 3, 5 (CGRP-encoding), and 6 of the first hCT/CGRP gene, but sequences closely related to exon 4 (CT-encoding) could not be demonstrated. Southern blot hybridization analysis of DNA from human-rodent somatic cell hybrids showed that the second hCT/CGRP gene is located in the q12-pter region of chromosome 11. The first hCT/CGRP gene has previously been assigned to the p13-p15 region of chromosome 11.

Animals↗

The human gene encoding insulin-like growth factor I is located on chromosome 12.

A cDNA probe corresponding to mRNA encoding human somatomedin-C/insulin-like growth factor I (IGF-I) was used for the chromosomal assignment of the IGF-I gene. Southern-blot hybridization analysis of DNA from human-Chinese hamster somatic cell hybrids showed that the IGF-I gene is located on chromosome 12. Comparison of the chromosomal assignments of the IGF-I gene and two other members of the insulin gene family, with three c-ras oncogenes, reveals a remarkable association of the two gene families.

Animals↗

Localization of the polymorphic human calcitonin gene on chromosome 11.

A molecular probe containing a 584 base pairs sequence corresponding to part of the human calcitonin mRNA was used for the chromosomal assignment of the calcitonin gene. Restriction endonuclease analysis of DNA from human-Chinese hamster and human-mouse somatic cell hybrids, including some containing a translocation of human chromosomes, placed the calcitonin gene in the p14----qter region of chromosome 11. Analysis of human DNA showed that the calcitonin gene has a polymorphic site for restriction endonuclease TaqI.

Animals↗

Multiple endocrine neoplasia syndromes.

The multiple endocrine neoplasia (MEN) syndromes are characterized by autosomal dominant inheritance with a high degree of penetrance but varying expression. This review gives a classification of these syndromes and a short summary of the historical background. The pathogenesis of the disease and its possible origin in the APUD cell system are discussed together with the mechanisms underlying normal and ectopic hormone production by MEN tumors on the basis of recent findings in molecular endocrinology. The natural history and the clinical manifestations of the different syndromes are described. The sensitivity and discriminative capacity of the tests used to detect the syndromes in an early stage are compared. The choice of therapy and criteria for the timing and extensiveness of treatment are also considered. Lastly, problems associated with the ethical and legal aspects of screening, central registration, and monitoring of relatives at risk are described.

APUD Cells↗

Expression of the proopiomelanocortin gene in human medullary thyroid carcinoma.

mRNA isolated from medullary carcinoma of the thyroid (MTC) in six patients with the inherited multiple endocrine neoplasia syndrome type 2 and cervical metastases in two patients with sporadic MTC was screened for the presence of calcitonin and proopiomelanocortin (POMC) related sequences by blot hybridization analysis. All tumors were found to contain mRNA hybridizing to a calcitonin-specific probe. However, POMC-related sequences were detected only in RNA preparations purified from the metastases of MTC. Compared with the POMC mRNA occurring in the human pituitary gland, the size of the RNA species hybridizing to the POMC-specific probe was larger in the metastases of both of the patients investigated. cDNA complementary to mRNA from one of the metastases was cloned into pBR 322. From this library two plasmids were isolated containing inserts which were completely homologous to a sequence of 190 nucleotides from the 3'-end of human pituitary POMC mRNA. In conclusion, 1) hybridization and nucleotide sequence analyses demonstrate that the POMC gene is expressed in MTC metastases; 2) the observed length difference between MTC and pituitary mRNAs suggests differences in expression or processing; 3) no expression of the POMC gene was found in six primary tumors.

Adolescent↗

Calcitonin gene related peptide coding sequence is conserved in the human genome and is expressed in medullary thyroid carcinoma.

Nucleotide sequence analysis of part of the human calcitonin (hCT) gene revealed the presence of a region with 90% homology to the region in the corresponding rat gene encoding calcitonin gene related peptide (CGRP). Analysis of RNA isolated from human medullary thyroid carcinoma (MTC) indicated that in these tumors mRNA hybridizing to hCT specific probe, mRNA hybridizing to hCGRP specific probe and larger RNA species hybridizing to both hCT and hCGRP probes occur. These results suggest that alternative splicing of the primary transcripts of the human CT gene may result in hCT or hCGRP mRNA.

Adult↗

Common precursor molecule as origin for the ectopic-hormone-producing-tumour syndrome.

When messenger R.N.A. (m-R.N.A.) extracted from various hormone-secreting tumours was injected into Xenopus eggs, the translation products in all cases proved to be a protein of molecular weight 65 00. Analysis by polyacrylamide-gel electrophoresis and specific precipitation reactions with antibodies showed a striking similarity between the various proteins. When translation products of m-R.N.A. from calcitonin-secreting medullary thyroid carcinoma (M.T.C( and the non-secreting anaplastic form of M.T.C. were incubating with specific enzyme systems (the microsomal fraction) from both types of tumour, enzymes from anaplastic M.T.C. had no effect on the translation products, whereas enzymes from differentiated M.T.C. degraded the translation products from both differentiated and anaplastic M.T.C. The results support the hypothesis that the primary gene product of all the different types of carcinoma cell studied is a single large protein (a hormone precursor or prohormone) containing different specificities. The specific enzyme system in each carcinoma cell probably selects the specific hormone liberated from this primary protein.

Adenocarcinoma↗