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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic hepatitis B virus (HBV) infection is etiologically related to human hepatocellular carcinoma (HCC). Most HCCs contain integrated HBV DNA in the liver cellular DNA, suggesting that the integration may be involved in carcinogenesis. From a comparison of a single HBV integration site present in a hepatoma with the corresponding unoccupied site in the non-tumourous tissue of the same liver, we have shown that HBV DNA inserted in a putative cellular exon with striking similarity to the DNA-binding domain of the thyroid/steroid hormone receptors. The corresponding cDNA has been isolated (hap gene) and shown to encode the retinoic acid receptor. In the original patient, integration took place so that the first codons of the viral surface protein gene became fused in frame with most of the hap gene. Because retinoic acid is known to regulate the transcription of target genes crucial for cellular growth and differentiation, it is most probable that consequent to the HBV insertion, hap, usually transcribed at a very low level in normal hepatocytes, became inappropriately expressed as an altered chimaeric retinoic acid receptor, thus contributing to the cell transformation. These results strongly support the possibility that HBV may play a direct role in liver carcinogenesis by insertional mutagenesis.
Mol Biol Med 1990 Jun
PMID:Hepatitis B virus as an insertional mutagene in a human hepatocellular carcinoma. 217 Aug 9

Natural and synthetic retinoids are potent inhibitors of experimental carcinogenesis in animals and cause reversion of premalignant lesions in humans. In the model C3H 10T1/2 cell system, retinoids enhance postconfluent growth control, reversibly inhibit carcinogen-induced transformation, and enhance gap junctional intercellular communication. These effects are highly correlated. 10T1/2 cells were found to express low levels of connexin 43, a gap junctional protein first found in the heart. After treatment of confluent 10T1/2 cells with the synthetic retinoid tetrahydrotetramethylnapthalenylpropenylbenzoic acid (TTNPB), levels of connexin 43 mRNA and protein increased within 6 h of treatment, while elevation of junctional communication was detected within 12-18 h. The maximally effective concentration of TTNPB (10(-8) M) caused an approximate 10-fold elevation of connexin 43 gene transcripts after 72 h. Indirect immunofluorescence microscopy using a polyclonal antibody to the synthetic C-terminal region of connexin 43 demonstrated that TTNPB induced many fluorescent plaques in regions of cell-cell contact. These results provide a molecular basis for the retinoid-enhanced junctional communication in 10T1/2 cells. It is proposed that one action of retinoids is to modulate the intercellular transfer of signal molecules. These could mediate many of the physiological actions of retinoids on growth control and carcinogenesis.
Mol Carcinog 1990
PMID:Retinoid-enhanced gap junctional communication is achieved by increased levels of connexin 43 mRNA and protein. 217 4

Mouse mammary epithelial cells can be transformed in primary cultures to preneoplastic and neoplastic states when treated with N-methyl-N-nitrosourea (MNU). Mammary carcinomas arising from MNU-induced hyperplastic alveolar nodules (a type of mouse mammary preneoplastic lesion) contained transforming c-Ki-ras genes when examined by the NIH 3T3 focus assay. Hybridization of allele-specific oligonucleotides to c-Ki-ras sequences amplified by the polymerase chain reaction demonstrated the presence of a specific G-35----A-35 point mutation in codon 12 in each of the NIH 3T3 foci as well as the mammary carcinomas. This mutation resulted in the substitution of the normal glycine with an aspartic acid. Furthermore, this mutation in the c-Ki-ras proto-oncogenes was also detected in 9 of 10 hyperplastic alveolar nodules. These results demonstrate that the specific c-Ki-ras mutation is a preneoplastic event in MNU-induced mouse mammary carcinogenesis.
Mol Cell Biol 1990 Apr
PMID:Transforming c-Ki-ras mutation is a preneoplastic event in mouse mammary carcinogenesis induced in vitro by N-methyl-N-nitrosourea. 218 Dec 80

A model describing the mechanism of linear integration of cellular and viral DNA is proposed. The possible role of cellular DNA integration in the process of human carcinogenesis is considered.
Mol Biol (Mosk)
PMID:[Mechanism of integration of cellular and viral DNA. Possible role of integration in the carcinogenesis]. 219 81

The objective of this study was to determine whether activation of c-Ki-ras occurs in carcinogen-induced rat pancreatic tumors. DNAs from 27 samples, which included adenomas, carcinomas in situ, and adenocarcinomas arising in azaserine-treated rats and corn oil-gavaged rats along with a nafenopin-induced rat pancreatic adenocarcinoma were examined for mutation of c-Ki-ras at codons 12, 13, and 61 by using the polymerase chain reaction. Our results indicate that activation of c-Ki-ras is not a common event during pancreatic carcinogenesis in the rat.
Mol Carcinog 1990
PMID:Activation of c-Ki-ras not detectable in adenomas or adenocarcinomas arising in rat pancreas. 219 2

Male F344 rats were fed N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) for up to 4 wk, then were given the basal diets (Prolab 3200 or AIN-76A) with or without 5% sodium saccharin for up to 100 wk. Eleven transitional cell carcinomas (TCCs), one undifferentiated carcinoma, and two sarcomas of the urinary bladder were examined for the expression of ras gene product, p21, by immunohistochemical staining and western blot analysis. Point mutation in codons 12 or 61 of the Ha-ras genes amplified by polymerase chain reaction was examined by a slot-blot screening procedure using allele-specific oligonucleotide probes. Immunohistochemical staining showed enhanced immunoreactivity with the antibody to ras p21 in seven TCCs and one undifferentiated carcinoma. Western blot analysis showed faster migration of the p21 band in 6 of 11 TCCs. Oligonucleotide hybridization revealed the point mutation in codon 12 of Ha-ras gene (GGA----GTA in 1 TCC) and in codon 61 (CAA----CGA in 5 TCCs and CAA----CTA in 1 TCC). Two mutations in codons 12 and 61 coexisted in one tumor, which were found to be present in different Ha-ras alleles. The incidence of Ha-ras gene mutations were similar in groups treated with (3 of 6) or without (3 of 8) sodium saccharin. These results suggest the involvement of activated Ha-ras gene in rat urinary bladder carcinogenesis induced by FANFT.
Mol Carcinog 1990
PMID:Point mutation in codons 12 and 61 of the Ha-ras gene in rat urinary bladder carcinomas induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. 220 84

Based on literature data and on the results of the authors' investigation, the analysis of the transforming growth factor beta action as an inhibitor of proliferation of normal and tumor cells was carried out. The possible mechanisms of modulation of this action by other growth factors and by the cultivation conditions were considered. An attempt was made to determine the role of the transforming growth factor beta in the system of regulators of cell proliferation on the early stages of ontogenesis and during carcinogenesis.
Mol Biol (Mosk)
PMID:[Transforming growth factor beta--a new type of inhibitor of proliferation of normal and tumor cells]. 225 Jun 81

Steroid hormones, regulators of cell differentiation and proliferation, are believed to play a role in carcinogenesis. Glucocorticoid hormones in particular modulate the expression of a number of proteins implicated in this process. We have investigated the effect of dexamethasone on two cell lines derived from a colon carcinoma, which differ by their tumorigenicity. Dexamethasone was found to inhibit growth of both the progressive (PROb) and the regressive clone (REGb). Upon hormonal treatment, glucocorticoid hormones induced fibronectin secretion by the two clones, whereas PROb cells were found to secrete an additional Mr approximately 43,000 protein. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The progressive cells (PROb) contained more specific glucocorticoid-binding sites (approximately 170,000 sites per cell) than the regressive ones (REGb cells; approximately 100,000 sites per cell). In both clones, the receptor was associated with the Mr approximately 90,000 heat shock protein to yield large complexes (Stokes radius Rs approximately 7.5 nm), which were dissociated to the same extent upon heat- and salt-treatment. The steroid- and DNA-binding unit of the receptor, characterized under denaturing conditions using an anti-receptor monoclonal antibody was found to be more degraded in the progressive cell line.
J Steroid Biochem Mol Biol 1990 Oct
PMID:Glucocorticoid effects and receptors in two rat colon carcinoma cell lines differing by their tumorigenicity. 226 53

The gut hormone cholecystokinin exerts various actions on the gastrointestinal tract, including the regulation of growth. The hormone has been reported to induce hypertrophy and hyperplasia of the pancreas and to enhance chemically-induced pancreatic carcinogenesis in animals. Stimulation of endogenous cholecystokinin secretion through the induction of deficiency of intraintestinal proteases and bile salts by trypsin-inhibiting nutrients, bile salt-binding drugs or surgical intervention is also capable of stimulating growth and tumour development in the rat. In man, factors suggested to increase the risk of pancreatic cancer, such as a high-fat and high-protein diet or gastrectomy, are known to stimulate plasma cholecystokinin secretion. Receptors for cholecystokinin have been demonstrated on human pancreatic adenocarcinomas, and cholecystokinin has been demonstrated to enhance the growth of xenografted pancreatic cancer and to inhibit growth of gastric and bile duct cancer. The recently developed cholecystokinin-receptor antagonists inhibit not only pancreatic growth but also pancreatic carcinogenesis in animals. These new drugs may be valuable new tools for inhibiting pancreatic cancer growth in humans.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Cholecystokinin and gastrointestinal cancer. 228 82

While steroid hormones act as endocrine effectors of growth and development of normal breast and of carcinogenesis and progression of malignant breast, recent evidence suggests that local hormonal effectors also exist. These are the growth regulatory growth factors. This article summarizes current status of our understanding of structure and function of growth factors secreted by the normal and malignant mammary epithelium. While growth inhibitory factors and their receptors generally suppress development of the transformed phenotype and promote differentiation, growth stimulatory factors and their receptors may be necessary for both normal proliferation and early stages of malignant progression of breast cancer. Overexpression of two receptors, c-erbB-2 and EGF receptor, have also been associated with poor prognosis in the clinical disease.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Stimulatory and inhibitory growth factors and breast cancer. 228 93


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