Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bcl-1 gene maps to chromosome 11q13 and has recently been shown to be a member of the cyclin gene family. Amplification of the chromosome region containing bcl-1 occurs frequently in breast cancer, squamous cell cancer, and other tumor types. We have hypothesized that amplification results in altered expression of the bcl-1 gene, contributing to carcinogenesis. In this work, we studied bcl-1 gene amplification and expression in a panel of human cell line. bcl-1 is expressed in all cell lines studied. The level of expression tends to be higher in amplified cell lines. We also screened these cell lines for int-2 and hst-1 expression, genes which are frequently coamplified with bcl-1. No int-2 expression was detected, and the two cell lines expressing hst-1 were unamplified. Our data provide support for the importance of bcl-1 in carcinogenesis.
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PMID:Amplification and expression of the bcl-1 gene in human solid tumor cell lines. 156 16

Nonrandom patterns of chromosome abnormality in tumors are providing clues to the location of oncogenes and their activation mechanisms. Studies of translocations in Burkitt's lymphoma cells have shown that the c-myc proto-oncogene is consistently juxtaposed with a rearranged and transcriptionally active immunoglobulin gene locus, with resultant myc gene deregulation. In other B cell tumors, translocations appear to bring previously unrecognized oncogenes (bcl-1, bcl-2) into similar association with the immunoglobulin heavy-chain locus. T cell receptor genes may also "activate" known and unknown oncogenes after chromosome translocation. In chronic myelogenous leukemia, the translocated c-abl oncogene forms a "hybrid" gene in its new location on the Philadelphia chromosome, with altered function. Gene amplification units, seen as cytogenetically homogeneous staining regions in chromosomes or as double-minute bodies in metaphases, can represent multiple copies of oncogenes and be important in late stages of tumor progression. Other significant alterations in gene dosage, recognized as gain or loss of all or part of a specific chromosome, also occur in human neoplasms, but their specific role in carcinogenesis is largely undefined.
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PMID:Chromosomal approaches to the molecular basis of neoplasia. 332 6

Squamous cell carcinomas (SCCs) of the mouse skin, as well as several types of preinvasive carcinoma precursor lesions, were produced by complete carcinogenesis protocols with benzo[a]pyrene (B[a]P). Groups of mice were studied histologically at several time points. Tumors and precursor lesions were systematically counted on microscope slides. The main feature of tumor development using this ubiquitous human carcinogen was the sequential appearance of in situ flat lesions with progressive degrees of dysplasia. These changes, preceding the development of SCCs, were observed 20 weeks after beginning the carcinogen treatments. At this time point, in situ lesions outnumbered SCC approximately 10:1 at the higher total carcinogen dose examined. Ten weeks later, this ratio was approximately 1:1. With the lower total carcinogen dose protocol, progression was delayed since at 27 weeks preinvasive lesions outnumbered SCCs approximately 8:1. In addition to the in situ lesions, papillomas and keratoacanthomas were noted with the high B[a]P dose protocol, but tended to disappear at the end of the experiment, also indicating their probable role as SCC precursors. A study of histochemical markers showed that gamma-glutamyltranspeptidase (GGT) and keratin 13, although good markers of malignant changes in early papillomas produced by two-stage carcinogenesis protocols, were mainly negative in dysplastic lesions produced by complete carcinogenesis with B[a]P. Immunohistochemical detection of p53 showed that 50% of SCCs were positively stained, whereas only 3% of in situ lesions were p53 immunoreactive. Similarly, 62% of SCCs were immunohistochemically positive for cyclin D, but no precursor lesions were positive. Molecular analysis of the tumors showed the absence of H-ras mutations. No amplification of the cyclin-D-1 gene was detected in eight SCCs examined. Collectively, these findings indicate that preinvasive in situ lesions are frequent during early stages of carcinogenesis when B[a]P is used in a complete carcinogenesis protocol. Although the absence of p53 immunoreactivity in this mouse model differs from the observed changes in human premalignant squamous lesions, the sequence of morphological changes and the final incidence of p53 and cyclin D staining abnormalities are very similar to the well-known alterations that take place during human squamous carcinogenesis.
Carcinogenesis 1995 Jul
PMID:Positive immunohistochemical staining of p53 and cyclin D in advanced mouse skin tumors, but not in precancerous lesions produced by benzo[a]pyrene. 754 77

p16INK4a and p15INK4b are cell cycle regulators that specifically bind to and inhibit the cyclin D-dependent kinases, cdk4 and cdk6. Because these genes undergo frequent deletions and/or mutations in various human cancers, we examined the status and expression of the cognate mouse cdk inhibitors in a panel of 29 cell lines, as well as in 12 primary tumors, representing different stages of mouse skin carcinogenesis. Deletion of p16INK4a and/or p15INK4b was seen in 8 of 10 cell lines derived from spindle carcinomas, the most advanced stage of skin carcinogenesis. Five showed deletion of both genes, and three had independent deletions of p16INK4a or p15INK4b, but in those retaining p16INK4a, expression of the protein was not detected. By contrast, none of 19 more differentiated squamous cell lines exhibited such deletions. In several cases, primary tumor DNA was available, and two spindle tumors showed the same deletion pattern as observed in the corresponding cell lines. In apparent contrast, comparison of two clonally related squamous and spindle cell lines derived from a single carcinoma showed unusually high levels of p16INK4a and p15INK4b only in the invasive spindle cells. Therefore, deletion or altered regulation of p16INK4a and p15INK4b occur concomitantly with the loss of differentiation associated with the late spindle stage of tumor progression in mouse skin.
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PMID:Deletion and altered regulation of p16INK4a and p15INK4b in undifferentiated mouse skin tumors. 758 67

It has recently become clear that cyclin-dependent kinase (cdk) complex regulates the cell cycle by phosphorylating Rb protein, a tumor suppressor protein. It is likely that this complex is a target of various growth factors and anti-growth factors (UV, TGF-beta etc.) in keratinocyte (KC). It has also been suggested that abnormalities in the cell cycle regulating mechanism such as increased activity of cyclin-cdk due to mutation of p53, a tumor suppressor gene, and overexpression of cyclin D may be concerned with carcinogenesis of KC. Thus, recent studies indicate that the cyclin-cdk complex is a common target of proliferation and carcinogenesis in KC.
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PMID:Cell cycle regulators in the keratinocyte (cyclin-cdk). 775 27

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

Gene amplification in stomach and oesophageal cancers was reviewed. In stomach cancers, two receptor type tyrosine kinases, c-erbB-2 and K-sam, are frequently amplified and overexpressed. c-erbB-2 seems to be preferentially amplified in well-differentiated, and K-sam in poorly-differentiated, gastric adenocarcinomas. 11q13 genes are amplified in about 50% of the oesophageal cancers. These genes include hst-1, int-2 and cyclin D/prad1, all of which are mapped to chromosome 11 at band q13. Although hst-1 and int-2 are usually not expressed despite amplification, elevated transcription of the cyclin D gene is accompanied by its amplification, suggesting a role of a G1 cyclin in oesophageal carcinogenesis.
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PMID:Amplified genes in cancer in upper digestive tract. 809 12

Recent evidence from molecular biology studies of the cell cycle machinery suggests that, apart from oncogenes and tumor suppressor genes, the genes encoding the key cell cycle regulatory proteins could serve as additional targets for oncogenic mutations involved in the multistep process of carcinogenesis. In an attempt to identify such potential cancer-associated aberrations of the cell cycle regulators, the expression of cdc2 and cdk2 kinases, as well as cyclins A, B1 and D1, was analyzed by immunoblotting in a panel of more than 40 human cancer cell lines derived from 17 different tumor types. The expression of cdc2, cdk2, cyclin B1 and cyclin A polypeptides was detectable in all lines examined, and moderate variation in protein level does not provide evidence for any obvious abnormalities in the cancer cell lines studied. The application of a series of novel monoclonal antibodies (Mab) to human cdc2 revealed the existence of an intriguing protein, designated p37, immunologically and structurally related to cdc2, which is strongly and selectively expressed in about 50% of the cancer cell lines. In contrast to cyclin A, which has also been implicated in tumorigenesis, we found pronounced variation in abundance of the cyclin D1 protein. Our data suggest that dysregulation of cyclin D1 (a candidate bcl-1, PRAD1 oncogene) can be involved in the pathogenesis of some additional tumor types (e.g., sarcomas and neuroblastomas) besides those reported for amplification and/or mRNA overexpression of this oncogene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular pathology of the cell cycle in human cancer cells. 831 19

Abnormality of the molecules regulating the cell cycle has been shown to lead cells to transformation. Recently, overexpression of cyclin D protein, one of the G1 cyclins, and the abnormality of the retinoblastoma gene have been found in various human cancers. We analyzed the expression of cyclin D, retinoblastoma gene product (pRB) and p53 in actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) by immunohistochemistry to elucidate the role of these molecules in keratinocyte carcinogenesis. In the normal epidermis, a few cyclin D positive cells were seen mainly at the basal layer. In 11 seborrheic keratoses, no overexpression of cyclin D was observed. Twelve of 26 AKs (46%) and 27 of 45 SCCs (60%) showed cyclin D overexpression. A few pRB positive cells were seen in the basal layer and in the suprabasal spinous layer of the normal epidermis. An abnormality of pRB, loss of expression, was seen in 2 of 26 AKs (8%) and 7 of 45 SCCs (16%). p53 protein was positive in 12 of 26 AKs (46%) and 24 of 45 SCCs (53%). Forty-five SCCs examined were divided into 22 ultraviolet (UV)-related SCCs and 23 UV-unrelated SCCs. Though UV-related SCCs showed a significantly higher incidence of p53 positivity, as previously reported by us, no significant difference in cyclin D overexpression and loss of the pRB expression was observed between UV-related and UV-unrelated SCCs. These results suggest that cyclin D overexpression is frequently involved in keratinocyte carcinogenesis and that this is an early event, as well as p53 abnormality. In addition, abnormality of the retinoblastoma gene is also related to epidermal cell carcinogenesis, though the frequency is relatively low.
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PMID:Cyclin D and retinoblastoma gene product expression in actinic keratosis and cutaneous squamous cell carcinoma in relation to p53 expression. 859 75

The growth and tumorigenicity of murine lung cancer cells transfected with an antisense cyclin D1 construct were evaluated in studies pertaining to mouse lung carcinogenesis. This antisense construct inhibited the expression of cyclin D in these cells, significantly reducing both their in vitro proliferation and tumorigenicity in nude mice relative to control cells. These data may have implications regarding the treatment of human neoplasms of aerodigestive tract origin that either overexpress the cyclin D oncogene or exhibit mutations that influence cell cycle progression via cyclin D-dependent mechanisms.
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PMID:Inhibition of lung cancer proliferation by antisense cyclin D. 872 12


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