Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies showed that the human monocytic leukemia cell line THP-1 can be induced to undergo monocytic differentiation by tumor promoting phorbol esters (TPA), suggesting that protein kinase C (PK-C), the primary binding site of TPA, may play a role in the control of monocytic differentiation: The effect of exogenous phospholipase C (PLC) on THP-1 cells was investigated. Within 24-48 hr, PLC induced over 40% of THP-1 cells to undergo monocytic differentiation as manifested by adherence, growth arrest, functional expression, morphological changes and expression of c-fms gene which encode for M-CSF receptors. Compared to TPA, however, the inducing activity of PLC was weaker, slower and not as effective. PLC treatment also induced a transient expression of c-fos proto-oncogene prior to c-fms expression. On the contrary, the level of c-myc RNA, which is constitutively expressed in THP-1 cells, was down-regulated 48 hr after PLC treatment. The PLC-induced monocytic differentiation in THP-1 cells was inhibited by staurosporine, a potent PK-C inhibitor, further suggesting that direct activation of the PK-C is one of the metabolic events essential for monocytic differentiation. It is postulated that in THP-1 cells the metabolic pathway transducing PK-C activation has been permanently blocked, thereby leading to uncontrolled proliferation without differentiation.
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PMID:Phospholipase C-induced monocytic differentiation in a human monocytic leukemia cell line THP-1. 149 32

We analyzed six different tissue DNA samples from a leukemic individual who received an injection of Thorotrast for alterations in proto-oncogene or tumor-suppressor gene structure. Our examination of the DNA indicated an alteration of the c-fms gene in the blood sample from this individual. This locus showed a deletion in which the 3' end of the deleted region maps between exons 11 and 12. In this particular case, the type of leukemia is unknown but myeloid leukemia is a neoplasm associated with individuals injected with Thorotrast. It is possible that the alteration in the c-fms gene of this individual is a consequence of the radiation exposure. No apparent alterations in the c-mos gene were observed in any of the tissues from the individual. This is in contrast to previous studies that described alterations in methylation patterns associated with the c-mos locus in radium-exposed individuals. A number of the individuals exposed to radium also had alterations of the retinoblastoma gene while no such alterations were observed in any tissue DNA samples from this Thorotrast case. It is possible that our inability to detect alterations of the c-mos and retinoblastoma gene may be attributable to the nature of alpha-emitting radionuclides or their distribution, or to the limited set of tissues available for analysis.
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PMID:Alteration of the c-fms gene in a blood sample from a Thorotrast individual. 152 6

Estrogen is thought to stimulate the proliferation of human breast tumors indirectly, through induced production of autocrine polypeptide growth factors. Constitutive production of such growth factors would lead to the loss of 17 beta-estradiol (E2)-dependence that is associated with progression of the disease. Our data, however, do not support this hypothesis and suggest that hormone-dependent breast tumor cell lines like MCF7 do not react to the growth factors which they produce. Moreover, we provide evidence that E2 directly stimulates proliferation by inducing, like many growth factors, the c-fos proto-oncogene. E2 by itself, however, is poorly mitogenic. This may be caused by the lack of induction of genes from the jun family, whose gene products are necessary for dimerization with the c-fos encoded protein, leading to an important step in growth factor signalling pathways; stimulation of TPA responsive element (TRE)-dependent transcriptional activity. In combination with insulin-like growth factors, efficient inducers of c-jun in these cells, E2 synergistically stimulates proliferation and TRE-activity. Constitutive TRE-activation may lead to loss of E2-dependence.
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PMID:Direct stimulation by estrogen of growth factor signal transduction pathways in human breast cancer cells. 152 51

A highly malignant human T-cell leukemia was identified by cell surface analysis as a member of the T-cell receptor (TCR) gamma delta lineage. Cytogenetic and molecular analysis showed a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on chromosome 14 and the distal end of chromosome 8 near the c-myc proto-oncogene locus. The gamma delta TCR of the leukemia blasts was functionally intact and could be activated to generate intracellular calcium flux and to target Fc receptor-mediated redirected tumor cell lysis. In addition, non-major histocompatibility complex restricted lysis of a limited target cell panel was shown by fresh leukemic blasts and by the in vitro-maintained leukemia cells that was comparable to known T-cell lines with natural killer-like activity. These data suggest that the T-cell leukemia potentially had in vivo functional cytolytic activity. However, whether this activity did contribute to the patient's clinical condition could not be determined.
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PMID:A gamma delta+ T-cell leukemia bearing a novel t(8;14)(q24;q11) translocation demonstrates spontaneous in vitro natural killer-like activity. 153 37

Six human colon tumor cell lines were analyzed for their constitutive levels of the c-myc protein. The nuclear proto-oncogene, c-myc, was detected as an expressed product in all of the human colon tumor cell lines analyzed. The poorly differentiated cell lines HCT116, RKO and C showed c-myc levels that averaged 2-fold greater than their well-differentiated counterparts, i.e., GEO, CBS and FET. When c-myc levels and responses to serum induction were analyzed in the presence of inducers of differentiation, i.e., dimethylformamide, retinoic acid, sodium butyrate and TGF-beta, distinct patterns of sensitivity and resistance emerged. Nuclear c-myc levels were reduced in all the colon cell phenotypes treated with dimethylformamide or sodium butyrate. Only the well-differentiated human colon tumor cell lines were responsive to transforming growth factor-beta. Only one of the human colon tumor cell lines (GEO) responded to retinoic acid. Increased levels of c-myc protein were found to correlate well with greater growth rates and with poor differentiation class. Similarly, a parallel sensitivity to down-regulation of c-myc levels and attenuation of c-myc induction curves for inducers of differentiation were observed in growth sensitive human colon tumor cell lines.
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PMID:Sensitivity of nuclear c-myc levels and induction to differentiation-inducing agents in human colon tumor cell lines. 154 Sep 46

The products of the myc proto-oncogene family have been suggested to carry functions important for cell proliferation, differentiation and neoplasia, but the molecular mechanisms of such biological effects have not yet been clarified. We have previously reported that the c-myc protein or protein(s) complexed with the c-myc protein bind to a specific sequence in the region upstream of the c-myc gene, where there exist an origin of cellular DNA replication (ori) and also a transcriptional enhancer. It was recently reported that the c-myc protein forms complexes with a novel helix-loop-helix leucine zipper protein (Max), and that the Myc-Max complex specifically recognizes a DNA sequence different from the sequence we have defined in the c-myc gene. In this report we examine the nuclear extract prepared from human Raji cells for binding to the two different sequences which have been reported as specific binding sequences for c-myc protein or c-myc protein complexes. The binding to one sequence was inhibited in the presence of excess amount of the other sequence, suggesting that the same protein(s) may be necessary for binding to either of the two sequences. Since binding to both sequences was cancelled by pretreatment of the Raji extract with an anti-c-myc protein antibody, it is suggested that proteins carrying myc-like antigenicity are necessary for efficient binding of the nucleoprotein complexes to the two distinct DNA sequences.
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PMID:Protein complexes bearing myc-like antigenicity recognize two distinct DNA sequences. 154 67

Twenty-three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto-oncogene mutations by mutation-specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin-fixed, paraffin-embedded tissue. Six of the 22 that were satisfactory amplified contained activating point mutations in codon 12 of K-ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K-ras, one had a GGT----GAT transition, four had GGT----GTT transversions, and one had both GGT----GAT and GGT----GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti-ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K-ras mutation. K-ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm.
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PMID:K-ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men. 156 75

From a total of 65 colorectal adenocarcinomas studied by cytogenetic methods, 33 were selected for the present study; in addition to other karyotypic anomalies, these 33 showed a loss of the short arm of chromosome 17. This loss was either the result of a deletion or rearrangement, or caused by the loss of a whole chromosome 17. The 17p- tumors were characterized by a high grade of karyotypic abnormality including a high incidence of cases with double minutes. A gain of chromosomes 2, 7, 19, and 20, and the loss of chromosome 18 and the Y-chromosome were the most frequent numerical anomalies associated with 17p-, as were structural changes of chromosomes 1 and 5. The most impressive difference in the pattern of proto-oncogene over-expression between the 17p- tumors and those without this anomaly was the significantly increased frequency of cases with c-erbB over-expression. Some significant, but also loose, associations were found between cytogenetic/oncogenetic and histopathologic or clinical features of these tumors. The patterns of genetic changes in cells of colorectal carcinomas may thus reflect the potential of the future development, rather than the present clinical features, of the respective tumor. Therefore, the character of the change seems to be more prognostic than diagnostic.
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PMID:Cytogenetic, oncogenetic, and histopathologic characteristics of colorectal carcinomas with 17p abnormalities. 157 67

Among environmental pollutants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is one of the most potent tumor promoters and teratogens known. The molecular mechanisms responsible for the biological activity of TCDD, however, remain largely unknown. In this report, we show that the first observable effects of TCDD in cultured murine hepatoma cells are a rapid, transient increase in Ca2+ influx and a minor but significant elevation of activated, membrane-bound protein kinase C. These changes are then followed by induction of the immediate early proto-oncogenes c-fos, jun-B, c-jun, and jun-D, and by large increases in AP-1 transcription factor activity. Induction of these changes by TCDD is delayed compared with that by phorbol esters, although the magnitude of the effects caused by both treatments is similar, and both induction processes can be blocked by staurosporine, a protein kinase C inhibitor. In cultured cells, proto-oncogene induction by TCDD appears to be independent of the presence of a functional aryl hydrocarbon (Ah) receptor or nuclear translocation protein. These results reveal early events that may lead to the elucidation of the molecular basis of TCDD-induced tumor promotion.
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PMID:Dioxin induces expression of c-fos and c-jun proto-oncogenes and a large increase in transcription factor AP-1. 160 50

The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S-phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph-node metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (greater than 5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node-positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p greater than 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes.
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PMID:c-myc amplification is an independent prognostic factor in postmenopausal breast cancer. 161 75


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