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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the expression of oncogene-encoded mRNAs in a rat model of colon cancer. In this model, rats are intrarectally administered several low doses of the direct-acting carcinogen, N-methyl-N-nitrosourea (MNU). Tumors, predominantly adenomas, develop 5-7 months following administration of the carcinogen, and many of these progress to carcinomas. Upon assaying the steady-state levels of oncogene-encoded transcripts in normal rat colon, we found that fos and N-myc are highly expressed; H-ras, K-ras, myc, myb, and neu messages are present at lower levels; and N-ras, abl, and raf mRNAs are absent. When we compared transcript levels in rat tumors to those in normal colons from the same animal, we observed a 2-4 fold increase in both myc- and H-ras-encoded mRNAs and a 2-7 fold increase in myb message, but no change in expression of any of the 7 other genes. To test whether this increased expression is related to tumor production or is simply a result of the more rapid cellular turnover observed in tumor tissue, the level of oncogene-encoded transcripts was assayed in colonic mucosae of rats given two treatments known to enhance cell turnover and DNA synthesis in the colon. Neither acute application of MNU nor a diet containing 1% cholic acid caused any change in the level of oncogene-encoded mRNAs in rat colons, thus suggesting that the increased abundance of myc, myb, and H-ras messages in tumors is associated with tumor formation. The enhancement of expression of these genes in adenomas, as well as in carcinomas, further suggests that these alterations occur relatively early during the tumorigenic process.
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PMID:Enhanced expression of oncogene-encoded mRNA in a rat model of colon cancer. 201 8

More than 60 breast cancer specimens were screened for their expression status of 25 different proto-oncogenes. The screening method is based on in vitro synthesis of a radioactive cDNA copied from the total cellular RNA of tumor tissue. This cDNA is hybridized to cloned oncogene probes which are immobilized to a GeneScreen membrane. Frequently multiple oncogenes were found expressed although expression levels were rather moderate. 25-30% of the analyzed tumors showed significant expression of either erbB, src, raf1, lck or H-ras. Although neu expression--an oncogene believed to be particular relevant as prognostic parameter for mamma carcinoma--was screened for most of the tumors with a heterologous gene probe, expression signals could be detected in about 20% cases. The only notable correlation with classical clinical parameters such as tumor size and proliferation stage, hormone receptor status and different DNA indices was the observation that tumors lacking the progesterone receptor frequently express multiple oncogenes. Advantages and limitations of the cDNA/dot-blot screening for oncogene expression are discussed.
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PMID:Expression of oncogenes in human breast cancer specimens. 201 53

The molecular genetics of human endometrial carcinoma have yet to be defined to any significant extent. Cell lines from 11 endometrial carcinomas were examined for alterations in proto-oncogenes that might predictably be present, based on existing data from the better-characterized human carcinomas of the uterine cervix, ovary, and breast. Codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes were examined for possible point mutations, and the c-erbB2/neu, c-myc, and epidermal growth factor receptor (EGFR) genes were examined for amplification or overexpression. Ras mutations were found in seven of 11 (64%) tumors, including three in codon 61 of Ha-ras (CAG----CAT) and four in codon 12 of Ki-ras (GGT----GAT in two and GGT----GTT in two). No evidence was found for amplification or overexpression of the c-erbB2 or EGFR genes in any tumor. One tumor contained amplified c-myc sequences and exhibited relative overexpression of c-myc. These data suggest that the amplification or overexpression of several proto-oncogenes frequently observed in other human gynecologic and breast tumors are not prevalent in endometrial carcinoma and that ras gene mutations are relatively common in this tumor type.
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PMID:Analysis of oncogene alterations in human endometrial carcinoma: prevalence of ras mutations. 206 24

In breast cancer, axillary lymph node invasiveness is the major prognostic factor in predicting relapse and metastasis. Nevertheless, since 30% of node-negative tumors also relapse, it is necessary to develop other independent prognostic factors. Oncogene amplification and the level of cathepsin D (cath-D), an acidic lysosomal protease produced and secreted in excess by breast cancer cells, have been proposed as additional prognostic factors. We have compared the cytosolic cath-D level and the amplification of three oncogenes: c-myc, neu-erb-B-2 and int-2 in 140 primary breast carcinomas and 64 axillary lymph nodes collected in 1987 and 1988 at the Cancer Center of Montpellier (Centre Paul Lamarque). None of the patients had previously received hormonal or chemotherapy. The cath-D concentration was measured with an immunoradiometric assay using monoclonal antibodies. DNA purified from the same samples was analyzed by a standard Southern blotting technique to estimate oncogene amplification. No correlation was found between the level of cath-D in the tumor and node invasiveness. Using a cut-off level of 60 pmol/mg protein, the status of cath-D was not correlated with neu-erb-B-2 and int-2 amplification and only correlated with c-myc amplification (P = 0.011). Both c-myc and cath-D are associated with cell proliferation, induced by estrogens in ER+ breast cancer, and constitutively produced in ER- breast cancer. The level of cath-D was significantly higher in the invaded lymph nodes (P = 0.04) than in the histologically non-invaded ones. Nevertheless, some non-invaded lymph nodes contained a high level of cath-D, as confirmed by immunoperoxidase staining. In conclusion, in breast cancer, a high cytosolic cath-D concentration is more frequent in tumors with c-myc amplification but is dissociated from neu-erb-B-2 or int-2 amplification, suggesting that the determination of these three markers will have an additional prognostic value.
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PMID:Cathepsin D assay in primary breast cancer and lymph nodes: relationship with c-myc, c-erb-B-2 and int-2 oncogene amplification and node invasiveness. 214 10

Cases of ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) of the breast were examined for expression of the protein product of the c-erbB-2 (neu, HER-2) oncogene using two different polyclonal antibodies via an avidin-biotin immunoperoxidase method on formalin- or Bouin'-fixed, paraffin-embedded tissue. Fifty-five percent (18/33) of DCIS and 10% (2/21) of ADH were positive. Significant c-erbB-2 expression in DCIS was generally divided on histologic grounds: ten of ten comedocarcinomas showed strong membrane staining, while only one of 14 small cell DCIS cases (micropapillary or cribiform patterns) showed immunostaining (which was weak and basilar in this single case). DCIS cases of mixed histology were strongly positive in areas of comedocarcinoma. In two of three cases of associated Paget's disease strong membrane staining was seen. The two c-erbB-2-positive ADH cases showed weak basilar staining akin to the small cell DCIS cases. Five cases of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) associated with DCIS or ADH were negative for c-erbB-2 expression. We conclude that comedocarcinoma in situ and Paget's disease frequently express the c-erbB-2 protein and are both histologically and biochemically distinct from ADH and small cell patterns of DCIS. We advocate precise subclassification of DCIS on histopathologic reports, particularly in view of reports that overexpression of the c-erbB-2 oncogene in infiltrating breast carcinomas may be associated with a poor prognosis.
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PMID:Immunohistochemical evaluation of c-erbB-2 oncogene expression in ductal carcinoma in situ and atypical ductal hyperplasia of the breast. 217 Sep 71

Although the morphology of neural tumors induced in rats by N-ethyl-N-nitrosourea (NEU) and related alkylating agents has been extensively investigated, their histogenesis and the molecular basis of malignant transformation are still largely unknown. This review gives an account of the interaction of neurocarcinogenic agents with cellular DNA, the possible role of promutagenic O6-alkyldeoxyguanine and their deficient repair by the cerebral O6-alkylguanine-DNA alkyltransferase. A new experimental model is described in which neural tumors are induced in fetal brain transplants. Pregnant rats received a single iv dose of NEU (50 mg/kg) on the 14th day of gestation. One day later, suspensions were prepared from the fetal forebrain and stereotactically injected into the caudoputamen of adult rats. After additional exposure to NEU of the host animals 8 days and 9 weeks post transplantation, all rats developed brain tumors within the neural graft. Histopathologically, all neoplasms were classified as olidogdendrogliomas. Other neoplasms typically induced by NEU transplacentally (astrocytomas, mixed gliomas, ependymomas) were absent. The selective induction of oligodendrogliomas indicates that neoplastic transformation in the nervous system can occur in a differentiated glial cell or a precursor cell committed to oligodendrocytic differentiation, and that transformation of a pluripotential stem cell is not necessary. Transplacental exposure of the donor fetuses to NEU alone, i.e., without additional postgrafting exposure, did not produce brain tumors in any of the experimental animals indicating that in the microenvironment of fetal brain transplants the multistep development of gliomas requires additional mutational events. Malignant schwanomas perinatally induced by NEU carry a point mutation in the transmembrane domain of the neu gene. The mode of oncogene activation in NEU-induced CNS gliomas has not yet been elucidated. We have used cerebral grafting techniques to study the effects of known oncogenes on the developing nervous system, taking advantage of efficient gene transfer by replication-defective retroviral vectors and of the extraordinary capacity of fetal CNS to differentiate in and fully integrate with the host brain. Rats carrying transplants exposed in vitro to the polyoma medium T-antigen developed endothelial hemangiomas in the graft which often led to fatal cerebral hemorrhage within 13-50 days after transplantation. Introduction of the viral src gene caused astrocytic and mesenchymal tumors after latency periods of 2-6 months. Following infection of fetal donor cells with a vector encoding the v-myc oncogene, only a single embryonal CNS tumor was observed whereas exposure to v-H-ras produced a low incidence of gliomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cellular and molecular aspects of neurocarcinogenesis. 219 39

The neu gene in rat neuro/glioblastoma was found to be activated by a single point mutation in the DNA sequence encoding the transmembrane region of the neu-encoded p185 protein. The human homologue of the rat neu gene, termed c-erbB-2 or HER-2, can also be activated in vitro by a similar mutation in the corresponding region. Although the human neu gene was shown to be amplified/overexpressed in a large portion of human breast and ovarian cancer, no reports indicate that the human neu gene is activated by a point mutation in human tumor. To study the possible point mutation of neu gene in human tumors, we characterized the genomic structure in the transmembrane region of human neu gene, which in turn allowed us to determine DNA sequence in this region directly following DNA amplification by polymerase chain reaction. We analyzed 7 tumor cell lines (2 breast cancer, 1 neuroblastoma, 1 rhabdomyosarcoma, and 3 glioma) and 11 tumor tissue samples (8 breast and 3 ovarian cancers). No mutation was found in the transmembrane region of human neu gene. Our results suggest that unlike the rat neuro/glioblastoma, the single point mutation in the transmembrane region of the human neu gene is a rare event in human tumors. In this study, we developed a technique for direct DNA sequencing of the transmembrane region of the human neu gene. This technique makes it possible to screen a large number of tumor samples.
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PMID:Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction. 220 83

Carcinogenesis is a multistep process, involving the irreversible conversion of a stem cell to a terminal-differentiation-resistant cell ("initiation"), followed by the clonal expansion of this cell ("promotion") and by the acquisition of other genetic alterations leading to malignancy ("progression"). The initiation and progression steps seem to be facilitated by mutagenesis. Promotion has been associated with agents and conditions that cause mitogenesis. Gap junctional intercellular communication, a fundamental biological process regulating cell growth and differentiation, has been postulated to play a major role in carcinogenesis. The hypothesis is supported by the fact that many cancer cells have some dysfunction in gap junctional intercellular communication, many tumor-promoting chemicals and several oncogenes (i.e., ras, src, mos, neu, but not myc) reduce gap junctional intercellular communication, and several growth factors (i.e., EGF, TGF-beta, bovine pituitary extract) inhibit gap junction function. This integrative concept postulates that chemical promoters, oncogenes coding for growth factors, receptors, or transmembrane signaling elements, and growth factors can isolate an initiated cell from the suppressing influence of surrounding normal cells by down-regulating the transfer of ions and small molecules through gap junctions.
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PMID:Modulation of intercellular communication during radiation and chemical carcinogenesis. 221 20

The neu oncogene codes for a cell surface protein that has a high degree of homology with the epidermal growth factor receptor. Amplification of this oncogene in breast carcinoma and ovarian carcinoma is correlated with a poorer prognosis. The c-myc oncogene codes for a DNA binding protein and is believed to regulate cellular proliferation. Sixteen primary endometrial adenocarcinomas were analyzed for c-myc and c-neu amplification. Eleven of sixteen tumor samples exhibited amplification of the neu gene. Four of these eleven patients died of disease an average of 16 months after diagnosis. The five patients without tumor amplification of the c-neu gene have been followed an average of 31.2 months without evidence of recurrent disease. Ten of fifteen tumor samples exhibited amplification of the c-myc gene. Five of the ten patients died of disease an average of 13.4 months after diagnosis. The remaining five patients have been followed for an average of 31.2 months and are free of disease. Six of the sixteen tumor specimens exhibited amplification of the both c-neu and c-myc genes, and four of these patients died of recurrent disease. Amplification of the c-neu or c-myc oncogene correlated with advanced-stage disease and poorly differentiated lesions, suggesting that oncogene amplification may predict biologically aggressive adenocarcinomas of the endometrium.
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PMID:Oncogene alterations in endometrial carcinoma. 222 49

Despite a considerable amount of information concerning chromosomal and molecular abnormalities found in gliomas in adults, relatively little is known regarding these abnormalities in pediatric brain tumors. We have analyzed DNA from 37 primary brain tumors and 4 tumor-derived cell lines for oncogene amplification. Probes utilized represent 11 known oncogenes (erbB1, gli, neu, myc, L-myc, N-myc, H-ras, K-ras, N-ras, sis, and src). Of 20 primary medulloblastomas studied, only one tumor was found to have erbB1 amplification. In contrast, of the 4 medulloblastoma cell lines studied, 1 had c-myc amplification, 1 had erbB1 amplification, and 1 had amplification of N-myc. Twelve glial brain tumors were analyzed, and only 1 case with amplification of the erbB1 oncogene was found. Other tumors studied include 1 meningioma, 2 ependymomas, 1 anaplastic ependymoma, and 1 cerebral primitive neuroectodermal tumor, none of which had oncogene amplification. These results suggest that oncogene amplification is relatively uncommon in primary medulloblastomas, but the frequency and diversity of oncogene amplification is greater in tumors that can be established as cell lines. The lower frequency of erbB1 amplification in glial brain tumors in children compared to adults is consistent with the generally lower grade of glial tumor histology seen in pediatric patients. However, the case with amplification of the erbB1 oncogene represented 1 of 2 cases of glioblastoma multiforme we studied, which suggests that pediatric glioblastoma multiforme may have a similar frequency of erbB1 oncogene amplification to glioblastomas seen in adults. Our results suggest that oncogene amplification is a relatively uncommon mechanism of oncogene activation in pediatric brain tumors, and they provide molecular evidence for heterogeneity in tumors classified as medulloblastomas.
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PMID:Oncogene amplification in pediatric brain tumors. 233 1


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