Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short-term cultures of normal human mammary epithelial cells were used to determine the extent to which c-myc, c-Ha-ras1, and c-erbB-2 proto-oncogenes were expressed in proliferating normal cells. This level of expression was compared with that of primary tumor cells, malignant effusion cells, or permanently established breast cancer cell lines. Pure preparations of epithelial organoids from seven different reduction mammoplasty tissue samples yielded proliferating normal epithelial cells upon short-term tissue culture. In every sample, proto-oncogene transcript levels increased upon short-term culture of the epithelial cells. These levels often exceeded by 10-fold the levels measured in uncultured organoids from the same tissue. In four of the seven cultured normal breast samples, at least one of the proto-oncogenes increased its expression to a level equaling or exceeding that found in a proliferating breast cancer cell line, MCF7. One effusion metastasis sample and two primary ductal adenocarcinomas were also examined for proto-oncogene expression. The effusion metastasis sample expressed high levels of c-erbB-2 messenger RNA, in accord with its amplified gene copy number; otherwise, the levels of proto-oncogene transcripts were low in unprocessed tumor and uncultured organoids, but they increased with proliferation of the tumor cells in culture. These results indicate that the variable expression of these proto-oncogenes observed in breast biopsy specimens needs to be controlled for cellular growth rate or proliferation index. Furthermore, these findings suggest that dysregulated proto-oncogene expression, rather than overexpression per se, needs to be evaluated as a possible mechanism contributing to the development of human breast cancer.
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PMID:Expression of c-myc, c-Ha-ras1, and c-erbB-2 proto-oncogenes in normal and malignant human breast epithelial cells. 257 2

We examined the expression of six proto-oncogenes in (i) whole rat liver and isolated liver cell populations during the course of hepatocarcinogenesis induced by a choline-deficient diet containing 0.1% ethionine and (ii) fetal rat liver at different stages of development. The abundance of c-Ki-ras, c-Ha-ras, and c-myc transcripts in polysomal polyadenylated RNA from liver cells increased by 2 weeks after the start of the carcinogenic diet. c-Ki-ras and c-myc expression remained elevated during the 35 weeks of the diet, whereas c-Ha-ras transcripts increased transiently. A primary tumor sampled at 35 weeks after the carcinogenic diet was started contained high levels of both c-Ki-ras and c-myc RNA. The abundance of c-src transcripts was unchanged throughout carcinogenesis; c-abl and c-mos transcripts were not detected in either preneoplastic or neoplastic livers. To determine which cell types within the liver contained proto-oncogene transcripts, we isolated hepatocytes, oval cells, and bile duct cells from normal and preneoplastic livers. The results indicate that proto-oncogenes are expressed differentially in these cell types during hepatocarcinogenesis and that the expression of c-Ki-ras and c-myc is high in oval cells throughout carcinogenesis. In developing livers, c-Ki-ras, c-Ha-ras, and c-myc transcript levels were high at 17 days of gestation but reached the low values characteristic of adult rat livers between 20 days of gestation and 3 days after birth.
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PMID:Expression of c-Ki-ras, c-Ha-ras, and c-myc in specific cell types during hepatocarcinogenesis. 258 Nov 26

A modified in-gel DNA renaturation technique, which detects DNA sequences amplified greater than 7-fold in human DNA, was used to analyze gene amplification in surgical specimens of primary and metastatic ovarian carcinomas. Amplified DNA sequences were detected in two of eight tumors. Hybridization of these samples with different oncogene probes revealed that both tumors contained an amplified Ki-ras gene, which in one case was coamplified with c-myc. In one of the tumors, Ki-ras was found to be amplified in both the primary tumor and three different metastatic nodules. No mutations at codons 12 or 61 of Ki-ras were detected in these tumors. No additional cases of Ki-ras or c-myc amplification were detected by Southern hybridization in the tumors that were found to be amplification negative by modified in-gel renaturation assays. These results indicate that gene amplification in ovarian carcinomas is likely to involve the Ki-ras oncogene.
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PMID:Association of Ki-ras with amplified DNA sequences, detected in human ovarian carcinomas by a modified in-gel renaturation assay. 264 92

In mice, endogenous retroviruses are known to be activated during the course of radiation osteosarcomagenesis. Using the Southern blotting procedure, we have studied the presence of somatically acquired proviruses in genomic DNA isolated from seven primary 90Sr induced osteosarcomas and one osteosarcoma cell line, 0-127a1, of the CF1 mouse strain. Specific hybridization probes demonstrated the presence of newly integrated ecotropic proviruses in four primary tumors. Probably, clonally integrated proviruses were present at distinct locations in different subpopulations of tumor cells, reflecting tumor heterogeneity. Genomic DNA isolated from cultured osteosarcoma cells contained different additional MCF-related proviruses. No proviruses were found integrated in the vicinity of c-myc, but a large domain containing the complete c-myc gene was found amplified in one primary tumor (greater than 22 kbp) and in 0-127a1 cells (greater than 39 kbp). Our data suggest that activated retroviruses are not essential for the development of radiogenic osteosarcomas in CF1 mice, but they might be responsible for the deregulated expression of a growth promoting gene in some bone tumor cells.
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PMID:Provirus integration and myc amplification in 90Sr induced osteosarcomas of CF1 mice. 283 3

Seventy lung tumors from 53 patients were analysed for alterations of myc family oncogenes, c-myc, N-myc and L-myc, to evaluate when activation of these genes occurs during tumor development. The 53 cases were 17 small cell carcinomas (SCCs), 18 adenocarcinomas, 12 squamous cell carcinomas (SqCs), 4 large cell carcinomas and 2 adenosquamous carcinomas. Either N-myc or L-myc was amplified in 4 of the 17 (one N-myc and 3 L-myc) SCCs (24%), while c-myc was amplified in 3 of the 12 SqCs (25%). In one SCC, amplification of N-myc was found in the primary tumor, a pulmonary hilar lymph node metastasis and a pleural metastasis, but not in a liver metastasis or a para-aortic lymph node metastasis. In one SqC, c-myc was amplified in a pleural metastasis and a lymph node metastasis, but not in the primary tumor. In 2 cases of SCCs, amplification or rearrangement of c-myc was detected only in the cell lines, but not in the original tumors taken from the same individuals. These results indicate that tumor cells were heterogeneous for amplification and rearrangement of myc family oncogenes, and suggest that activation of these oncogenes in SCCs and SqCs occurs not at the time of malignant transformation but during tumor progression.
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PMID:Heterogeneity of lung cancer cells with respect to the amplification and rearrangement of myc family oncogenes. 283 90

We report the expression of Ha-ras, fos, c-myc and N-myc mRNA in a human medullary carcinoma of the thyroid gland, both in primary tumor and lymph node metastasis, as demonstrated by in situ hybridization and Northern blot analysis. A significant difference in the oncogene expression in the primary tumor and the metastasis was not observed. Tumor tissue revealed a significant overexpression of Ha-ras, c-myc and N-myc mRNA as compared to the normal thyroid gland. The amount of fos mRNA expression in non tumorous thyroid gland did not significantly differ from tumor tissue, sis, fms and abl mRNA expression was not detectable in tumor tissue and non tumorous thyroid gland. We conclude, that the (over)expression of the oncogenes Ha-ras, c-myc and N-myc may be associated with initiation and progression of medullary thyroid carcinoma. Similar studies on additional cases of human medullary thyroid carcinoma will be necessary to reveal further information.
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PMID:Oncogene expression in a medullary thyroid carcinoma. 289 37

Activated c-Ki-ras with a point mutation (GGT to CGT) at codon 12, resulting in the substitution of arginine for glycine, was found in DNA from metastatic pancreatic adenocarcinoma in a lymph node. By means of restriction endonuclease length polymorphism with SacI digestion, we were able to demonstrate that the same point mutation of c-Ki-ras was present in the primary tumor and in metastases in lymph nodes. DNA from the normal spleen of the patient did not have this type of point mutation. Moreover, amplifications of 3- to 6-fold of the activated c-Ki-ras and 50-fold of c-myc were found in the primary tumor and the metastases in the two lymph nodes, indicating that point mutation had occurred at a relatively early stage of the tumor development, before amplification of the gene. This is the first clear demonstration of amplification of activated c-Ki-ras accompanied by amplification of c-myc in both primary and metastatic human tumors in vivo.
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PMID:Amplifications of both c-Ki-ras with a point mutation and c-myc in a primary pancreatic cancer and its metastatic tumors in lymph nodes. 300 77

We report the molecular analysis of primary cells from four cases of human B-cell malignancies each with an 8;14 chromosomal translocation involving the c-myc proto-oncogene and the immunoglobulin (Ig) gene cluster. In two cases of B-cell acute lymphocytic leukemia (B-ALL) the c-myc is truncated, rearranged into the Ig C alpha 1 locus and over-expressed in two abnormal mRNAs of approximately 2.0 and 2.8 kb. Conversely, in two cases of B-cell lymphoma progressed into leukemia the c-myc locus was translocated intact in its coding and 5'-flanking region into an Ig region different from C alpha 1, and over-expressed in two normal mRNA species. Cloning and sequencing of the breakpoint region on chromosome 14q+ from one of the two B-ALL cases showed that the myc gene is truncated 1077 nucleotides upstream from the translation start site, and rearranged in the opposite transcriptional orientation into an Ig class-switch segment approximately 4.8 kb upstream from the C alpha 1 gene. The c-myc anti-sense strand contains two class-switch recombination consensus sequences in the immediate boundaries of the breakpoint on chromosome 8: this allows us to postulate that an erroneous, class-switch-like recombination between Ig and myc sequences gave rise to the chromosomal translocation. Furthermore, we report 13 point mutations clustered in a region spanning from the first intron to the second exon of the translocated c-myc gene, five of which cause amino acid changes leading to an abnormal myc protein. This is the first evidence of mutations in a translocated c-myc in primary tumor cells.
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PMID:Translocation of c-myc into the immunoglobulin heavy-chain locus in human acute B-cell leukemia. A molecular analysis. 301 23

Chromosome translocations involving 8q24, the band to which c-myc has been mapped (Dalla-Favera et al., 1982), are a uniform finding in Burkitt's lymphoma (Bernheim et al., 1981). However, in only a minority of the tumors is the rearrangement of the c-myc locus sufficiently close to the gene to be detected with currently available probes (Dalla-Favera et al., 1983). Approximately 25% of diffuse large-cell lymphomas have also been reported to have translocations involving 8q24 (Mitelman, 1985), but there have been no reports of c-myc rearrangements in this form of non-Hodgkin's lymphoma. We have examined the structure of the c-myc locus in primary tumor tissue of 10 cases of diffuse large-cell lymphoma. In one patient, Southern blot analysis revealed additional c-myc fragments in the tumor DNA but not in the germ-line DNA. Southern blot analysis using probes from both the heavy- and light-chain immunoglobin loci showed that the myc rearrangement was unlikely to involve the immunoglobulin loci in this patient.
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PMID:Somatic rearrangement of the c-myc oncogene in primary human diffuse large-cell lymphoma. 301 98

Messenger RNA levels of the c-fos, c-myc, c-Ha-ras and c-Ki-ras genes were studied in 39 tissue samples obtained from 17 patients undergoing surgery for colon carcinoma and other colon diseases. DNA extracted from the same samples was studied by Southern analysis. The tissues were tumors and grossly normal mucosa from each case and in some instances benign polyps and metastases. Our results indicate: (1) that 50% of cases studied show an increase in expression of at least one of the oncogenes studied; (2) that over-expression is not random, some cases over-expressing several of the genes studied; (3) that the expression pattern of the oncogenes studied varies between primary tumor and metastases; (4) that amplification is a rare event, being limited to one instance in which c-myc was amplified in a metastasis; (5) that cases which exhibit high levels of mRNA in one or more genes studied correlate with biologically aggressive tumors; and (6) that "non-expressors" are at higher risk for local recurrence based on correlations with mucin histochemistry.
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PMID:Prognostic implications of expression of the cellular genes myc, fos, Ha-ras and Ki-ras in colon carcinoma. 304 May 97


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