Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that human bladder tumor cell lines may be adapted to grow in the complete absence of serum or any other growth supplement and that this can be explained on the basis of autocrine stimulation. In the present study we have extended the number of cell lines that could be established as serum-free cultures and found this capacity to be correlated with tumor malignancy. We also used the receptor blocking monoclonal antibody, mAb 528, to study its effect on tumor cell growth. Inhibition was observed in all of seven bladder carcinoma cell lines tested. A similar effect was observed in two colon carcinoma cell lines but not in a melanoma line. The results show that the EGFR is involved in autocrine growth stimulation and that the acquirement of autonomous growth capacity is likely to be an important factor in the oncogenesis of bladder tumors.
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PMID:The epidermal growth factor receptor is involved in autocrine growth of human bladder carcinoma cell lines. 921 46

We observed no association between neoplastic epithelial immunostaining for either amphiregulin (AR) or heregulin (HRG) and presence of ER, EGFR/ERBB-2 overexpression, nodal status, or disease recurrence in 34 breast carcinomas. However, stromal cell staining for both correlated with outcome; 29% of stromal cell AR - cases recurred vs. 85% for AR + cases (p = 0.001), and 41% of stromal cell HRG - cases recurred vs. 82% of HRG + cases (p = 0.01). We conclude that both HRG and AR have significant biologic roles in breast carcinoma growth or progression via mediation of host-tumor interactions which favor aggressive tumor behavior.
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PMID:Clinicopathologic analysis of amphiregulin and heregulin immunostaining in breast neoplasia. 928 19

104 surgery cases of non-small cell (NSLC) and small cell lung carcinoma (SLC) are studied. Oncoprotein bcl-2 is found in 49 out of 104 (47%) cases, more frequently in SLC (71%) than in NSLC (44%) and this correlated with carcinoma morphological malignancy. L-myc oncoprotein and EGFR were expressed practically in all cases, oncoprotein of the p53 mutated gene in 57% cases. The highest content of p53 was in SLC, large cell and poorly differentiated squamous cell carcinoma. Percentage of cells with mutated p53 statistically correlated with morphological malignancy of lung carcinoma. Oncoprotein of Rb gene was revealed in 51%, most frequently in squamous cell carcinoma (71%) and particularly in its well differentiated types. IGFII was found in 74% NSLC and in 100% SLC with cytoplasmic location in tumor cells; the level of expression was higher in SLC. IGFII 2 and 5 were more frequently observed in the foci of keratinization of squamous cell carcinoma. For the first time IGFP B3 was found not only in the cytoplasm but in the nuclei of tumor cells as well. There was a significant positive correlation between the content of IGFIBP3 in the nuclei of tumor cells and morphological malignancy (poor tumor cell differentiation, larger size and metastases). The mean number of proliferating Ki-67 positive cells was 24% but this figure was much higher (47%) in SLC. Squamous cell carcinoma is characterized by a more frequent and stronger expression of CD44 types 5 and 6 in the cytolemma and this may be considered as a marker of squamous cell differentiation of lung carcinoma.
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PMID:[Immunohistochemistry of biomolecular markers of lung cancer]. 948 14

In situ duct carcinoma (DCIS) is a heterogeneous group of lesions which has recently been subdivided into three types: well-differentiated (type I), intermediately differentiated (type II) and poorly differentiated (type III) DCIS. Fourteen cases of DCIS and 11 of DCIS with minimal invasion were analysed for mRNA levels of beta-actin, EGFR, c-cerbB2, MTS1, k-ras, RB, BRCA1, cyclin E, and c-myc genes. A microdissection technique was used on paraffin-embedded tissue. A statistically significantly higher expression of cyclin E oncogene and MTS1 tumor suppressor gene was seen in type III DCIS than in the other types, while no significant differences in the mRNA expression patterns of the other genes were observed. These data are consistent with the fact that poorly differentiated DCIS is a readily recognizable class of tumours that have a particularly aggressive behaviour and probably unique histogenesis.
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PMID:Molecular characterization of intraductal breast carcinomas. 950 54

Betacellulin (BTC) is a member of the EGF ligand family that directly binds to both EGFR and HER4 and induces the growth of certain epithelial cell types. Fusion proteins composed of the terminal 48 or 50 amino acids of mature betacellulin and a binding defective form of Pseudomonas exotoxin (BTC-TX48 and BTC-TX50, respectively), have been produced. BTC-TX50 induced tyrosine phosphorylation of both EGFR and HER4, whereas BTC-TX48 induced phosphorylation of HER4 but to a much lesser extent EGFR, indicating that the presence of two additional amino acid residues, Arg62 and Lys63, contribute to full kinase activity. BTC-TX50 was up to 300-fold more active at inhibiting protein synthesis than BTC-TX48 on cell lines expressing EGFR, most likely due to the >tenfold higher affinity of BTC-TX50. MDA-MB-453 breast carcinoma cells which express HER4 but not EGFR, were not sensitive to either BTC-TX form. These data indicate that despite the ability of BTC-TX to bind and phosphorylate HER4, it was only cytotoxic to cells expressing EGFR. The inability of BTC-TX to kill cells was likely due to its failure to internalize through HER4.
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PMID:Betacellulin-Pseudomonas toxin fusion proteins bind but are not cytotoxic to cells expressing HER4; correlation of EGFR for cytotoxic activity. 952 63

The Epstein-Barr Virus (EBV) LMP1 protein is frequently expressed in nasopharyngeal carcinoma and is essential for the transforming effects of EBV. Analysis of LMP1 genes isolated from tumor biopsies has revealed considerable sequence variation including deletion of amino acids 343-352. Several studies have suggested that this sequence variation could enhance the transforming potential of LMP1. LMP1 has profound effects on cellular gene expression mediated in part through activation of the NF-kappa B transcription factor. In addition, LMP1 engages the TRAF signaling pathway resulting in the induction of EGFR expression. In this study, the LMP1 proteins derived from the laboratory strain B95-8 and the NPC strain C15 were analysed for their ability to activate NF-kappa B and also to induce expression of the EGFR. The data suggest that the C15-LMP1 protein activates NF-kappa B more efficiently and induces higher levels of the EGFR. Analysis of chimeric LMP1 proteins indicates that the amino terminal 181 amino acids of C15-LMP1 confer this increased signaling capability, and that deletion of amino acids 343-352 does not affect these properties. Finally, these data provide evidence that five amino acid changes within the transmembrane domain in the C15-LMP1 protein lead to enhanced NF-kappa B activation and EGFR induction.
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PMID:The NPC derived C15 LMP1 protein confers enhanced activation of NF-kappa B and induction of the EGFR in epithelial cells. 958 84

Interleukin-6 (IL-6) is a cytokine that was initially recognized as a regulator of immune and inflammatory responses, but it also regulates the growth of many tumour cells, including prostrate carcinoma. Overexpression of the growth-factor receptors ErbB2/neu and ErbB3 has been implicated in the neoplastic transformation of prostate carcinoma. Here we show that treatment of the prostate cancer cell line LNCaP with IL-6 induces tyrosine phosphorylation of ErbB2 and ErbB3, but not ErbB1/EGFR. We also show that ErbB2 forms a complex with the gp130 subunit of the IL-6 receptor in an IL-6-dependent manner. This association is important because the inhibition of ErbB2 activity results in abrogation of IL-6-induced MAPK activation. Thus ErbB2 is a critical component of IL-6 signalling through the MAP kinase pathway. These data show how a cytokine receptor can diversify its signalling pathways by engaging with a growth-factor receptor kinase.
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PMID:Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. 959 Jun 94

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.
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PMID:Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. 970 36

Tumor necrosis factor (TNF)-alpha has a broad range of biological activities, which depend heavily on cell type and physiological condition. In a panel of human tumor cell lines we analyzed expression of the receptor tyrosine kinases EGFR, ErbB2 and ErbB3, and the response to TNF-alpha. Among the cell lines tested those resistant to TNF-alpha were found to express high levels of either EGFR, or ErbB2 and ErbB3. In TNF-sensitive breast and cervical carcinoma cells activation of EGFR or ErbB2 by the exogenous growth factors EGF and heregulin beta1 resulted in a significant increase in the number of cells surviving TNF-alpha treatment. In contrast, inhibition of EGFR activation in TNF-resistant breast carcinoma cells by the novel antagonistic anti-EGFR antibody 14E1 sensitized the cells to the cytotoxic effects of TNF-alpha. A bacterially expressed fusion protein consisting of a 14E1 single-chain (sc) Fv antibody fragment linked to human TNF-alpha retained TNF-alpha activity. This scFv(14E1)-TNF-alpha molecule localized specifically to EGFR on the surface of tumor cells and activated the NF-kappaB pathway in co-cultured T cells, as demonstrated by electrophoretic mobility shift assays.
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PMID:Activation of EGF receptor family members suppresses the cytotoxic effects of tumor necrosis factor-alpha. 982 42

The gene encoding human pancreatic ribonuclease 1 (hpRNasel) was fused with a gene encoding human epidermal growth factor (hEGF). The hybrid human protein was isolated from Escherichia coli inclusion bodies, refolded and purified to homogeneity. The fusion protein competed with 125I-hEGF for binding to hEGF receptors (EGFR) and had ribonucleolytic activities approaching those of hpRNase1. Several conformations having different enzymatic activities could be detected after reversed-phase high-performance liquid chromatographic analysis, the less hydrophobic molecules being the most active. The hybrid protein was specifically cytotoxic to A431, an EGFR overexpressing squamous carcinoma cell line, with an IC50 of approximately 10(-7) M. In contrast, recombinant hpRNase1 had an IC50 higher than 10(-4) M. A mixture of free hEGF and free hpRNasel was not more cytotoxic than hpRNasel alone and no cytotoxicity was detected in EGFR-deficient control cells. Taken together, these data suggest that this construct might be useful for targeted therapy of esophageal, lung and other squamous cell carcinomas and also breast cancers overexpressing EGFR, which correlate with a poor prognosis and cannot be cured by surgery alone. Engineering hybrid molecules with endogenous human proteins for targeted therapy may alleviate the dose-limiting immunogenicity and toxicity of conventional immunotoxins.
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PMID:Human pancreatic RNase1-human epidermal growth factor fusion: an entirely human 'immunotoxin analog' with cytotoxic properties against squamous cell carcinomas. 993 Jun 79


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