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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecules of the cadherin and integrin families involved in cell-cell and cell-matrix adhesion have been implicated in epithelial differentiation, carcinogenesis and metastasis. Having observed that a colon cancer cell line bound avidly to collagen type I, inducing integrin-triggered glandular differentiation, we investigated the regulation of integrin function in these cells. We modified a mammalian expression cloning system that used monoclonal antibody selection to clone cell surface molecules. Using attachment to collagen type I to select for adhesive phenotype, we isolated a complementary DNA clone that increases cell adhesion to components of the extracellular matrix. The corresponding gene (cell adhesion regulator, CAR) is located on the long arm of chromosome 16 (16q) and encodes a protein of 142 amino acids, which has an N-terminal myristoylation motif and a consensus tyrosine-kinase phosphorylation site at the C terminus. Removal of this tyrosine residue abolishes enhancement of cell-matrix adhesion. This gene may encode an adhesion signal transduction molecule that functions in the suppression of tumour invasion.
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PMID:Cloning and characterization of a gene that regulates cell adhesion. 842 14

We have compared expression of involucrin, E-cadherin and P-cadherin in cultures of normal keratinocytes and in five different lines derived from squamous cell carcinomas (SCCs), using Northern analysis and immunofluorescence. In normal keratinocytes there was an inverse correlation between P-cadherin and involucrin expression, whereas E-cadherin was expressed by both basal and terminally differentiating cells. In SCC lines involucrin expression was lower than in normal keratinocytes, and there was variable expression of P- and E-cadherin: E-cadherin mRNA levels tended to be lower in SCC lines than in normal keratinocytes, whereas P-cadherin levels were similar. Our results are consistent with observations of cadherin expression in vivo and suggest that the cultures provide a useful experimental model for investigating the role of cadherins in determining the spatial organization of normal and neoplastic keratinocytes.
Carcinogenesis 1991 Jul
PMID:Expression of E-cadherin, P-cadherin and involucrin by normal and neoplastic keratinocytes in culture. 207 May 2

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of gastric cancer. 767 88

Alterations in multiple oncogenes and multiple tumor suppressor genes are observed in human gastro-intestinal cancer. Among them, the most frequently implicated in malignancy and metastasis of esophageal carcinoma may be amplification and overexpression of the human cyclin D gene. In gastric carcinoma, amplification and abnormal expression of the c-met gene encoding receptor for hepatocyte growth factor (HGF) may contribute to the tumor progression and metastasis. Interaction between cadherin in c-met overexpressed tumor cells and HGF from fibroblast may play an important role in morphogenesis of two histological types of stomach cancer. During stomach carcinogenesis the clone having critical p53 mutations may expand selectively to make up a finally advanced stage of malignancy and show metastasis. In colorectal cancer, loss of heterozygosity of the RB, p53 and DCC genes is frequently associated with liver metastasis. Overexpression of nm23 may participate in carcinogenesis and the reduction in nm23 expression is involved in metastasis in gastric and colorectal cancers.
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PMID:[Metastasis related genes and malignancy in human esophageal, gastric and colorectal cancers]. 809 50

Desmosomes are junctions between epithelial, myocardiac, and certain other kinds of cells. They represent plasma membrane domains enriched in specific transmembrane glycoproteins, notably desmoglein (Dsg) and desmocollin (Dsc), both of which have recently been identified as members of the larger family of Ca(2+)-dependent cell adhesion molecules, the cadherins. Previously described forms of desmoglein have been isolated as proteins and cloned as cDNAs from epidermis and related stratified epithelia but have not been detected in the majority of other desmosome-containing tissues and cell culture lines. Here we present the complete cDNA-derived amino acid (aa) sequence of a different desmoglein polypeptide, termed Dsg2 (1069 aa, mol wt 116,760) and its precursor molecule (1117 aa, mol wt 122,384), which occurs in all human and bovine desmosome-producing tissues, tumors, and cell lines examined, epithelial as well as nonepithelial ones. We conclude that Dsg2, the largest molecule in this protein family, is the fundamental desmoglein common to all desmosome-possessing tissues, including simple epithelia and myocardium, and many cell cultures. Furthermore, in several tissues and cell lines Dsg2 is the only Dsg isoform detected so far. By contrast, the epidermal isoforms Dsg1 and Dsg3 are restricted to certain specialized epithelia, mostly stratified squamous ones. The importance of the junction-specific cadherin Dsg2 in tissue formation and carcinogenesis as well as in the development of autoimmune diseases of the Pemphigus type is discussed. In addition, we propose to use Dsg2 as a general marker common to all epithelial cells and tumors and to use the specific pattern of occurrence of Dsg and Dsc isoforms as an additional criterion for cell typing in tumor diagnosis.
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PMID:Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins. 814 88

Gene changes in multiple oncogenes, multiple growth factors and multiple tumor-suppressor genes are observed in stomach cancer. Among them, those most commonly implicated in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma are inactivation (mutations and allele loss) of the p53 gene, and activation (abnormal expression and amplification) of the c-met gene. Moreover, they occur at an early stage of stomach carcinogenesis. In addition, loss of heterozygosity (LOH) on chromosome 5q (APC locus) is frequently associated with well-differentiated adenocarcinoma. LOH on chromosome 18q (DCC locus) and LOH of the bcl-2 gene also are common events of well-differentiated adenocarcinoma. LOH on chromosomes 1q and 7q may be involved in the progression of well-differentiated adenocarcinoma. Conversely, the development of poorly differentiated adenocarcinoma, in addition to changes in p53 and c-met genes, requires reduction or dysfunction of cadherin. Overexpression of bcl-2 protein is observed in poorly differentiated adenocarcinoma or signet-ring cell carcinoma. Moreover, the K-sam gene is amplified preferentially in poorly differentiated adenocarcinoma of scirrhous carcinoma. K-sam amplification in scirrhous carcinoma often occurs independently of c-met gene amplification. LOH on chromosome 1p also is relatively common in poorly differentiated adenocarcinoma. Exceptionally, signet-ring cell carcinoma shares APC mutations. There are some differences in expression of the growth-factor/receptor system between well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma. Moreover, interaction between cell-adhesion molecules in tumor cells expressing c-met and hepatocyte growth factor (HGF) from stromal cells is linked with morphogenesis of two histological types of stomach cancer. Intestinal metaplasia and adenoma of the stomach also contain p53 mutations and K-ras mutations or tpr-met rearrangement. Taken together, different genetic pathways of stomach carcinogenesis may exist for poorly differentiated and well-differentiated stomach cancers. Some of the latter may develop by a cumulative series of gene alterations similar to those of colorectal cancer.
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PMID:Molecular mechanism of stomach carcinogenesis. 844 Jul 43

Analysis of the calcium-dependent cell adhesion molecule E-cadherin has led to the identification of catenins, which are necessary for cadherin function. Growing evidence that cadherins and catenins are subjected to genetic alterations in carcinogenesis makes it especially important to understand protein-protein interactions within the cadherin-catenin complex. Here we report the identification and analysis of the alpha-catenin binding site in plakoglobin (gamma-catenin). Using N- and C-terminal truncations of plakoglobin, we identified a domain of 29 amino acids necessary and sufficient for binding alpha-catenin. The alpha-catenin binding site is fully encoded within exon 3 of plakoglobin but only partially represented in Armadillo repeat 1. This suggests that exons rather than individual Arm repeats encode functional domains of plakoglobin. Site-directed mutagenesis identified residues in the alpha-catenin binding site indispensable for binding in vitro. Analogous mutations in beta-catenin and Armadillo had identical effects. Our results indicate that single amino acid mutations in the alpha-catenin binding site of homologs of Armadillo could prevent a stable association with alpha-catenin, thus affecting cadherin-mediated adhesion.
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PMID:Single amino acid substitutions in proteins of the armadillo gene family abolish their binding to alpha-catenin. 857 47

The scenario of multistep of stomach carcinogenesis differs depending on the two histological types, well differentiated adenocarcinoma and poorly differentiated adenocarcinoma, because the two types may have different genetic pathways. Genetic instability, reactivation of telomerase and abnormal transcript of CD44 including intron 9 are common events of both well and poorly differentiated type carcinomas. These occur at early stage of carcinogenesis, even in precancerous lesions such as intestinal metaplasia and adenoma. Inactivation of APC, activation of K-ras, amplification of c-erbB2, and allelic loss of DCC locus are associated with well differentiated type, while amplification of K-sam and functional loss of cadherin/catenin are characteristics of poorly differentiated type. HGF/c-met system plays a pivotal role in morphogenesis of both histological types through interaction with cell-cell adhesion molecules. Reactivation of telomerase or genetic instability may be an initial event for accumulation of multiple genetic alterations during the progression of stomach carcinogenesis.
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PMID:[Genetic alterations in stomach cancer]. 869 39

Genetic instability, alterations of tumor suppressor genes as well as activation of oncogenes and aberrant expression of growth factor/receptor system found in human stomach carcinogenesis are overviewed. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene and amplification of the cyclin E gene are common events of both well differentiated and poorly differentiated gastric carcinomas. K-ras mutations, c-erbB2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC, LOH of the bcl-2 gene and LOH at DCC locus are preferentially associated with well differentiated gastric cancer. On the other hand, microsatellite instability, reduction or loss of cadherin and catenins, K-sam and c-met gene amplification confer the development and progression of poorly differentiated or scirrhous gastric carcinomas. Interaction between cell-adhesion molecules in the c-met expressed cancer cells and hepatocyte growth factor from stromal cells is involved in morphogenesis of gastric cancer.
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PMID:[Multistep stomach carcinogenesis]. 892 Jun 75

A protein first identified by its association with cadherin cell adhesion molecules, beta-catenin, has been implicated in carcinogenesis. In a number of different types of cancer, signalling through beta-catenin is upregulated either by direct mutation of beta-catenin or loss of negative regulation by the APC tumor suppressor protein.
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PMID:Carcinogenesis: a balance between beta-catenin and APC. 921 Mar 68


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