Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occurs in several cultured tumor cell lines and in certain human malignancies. Placenta growth factor (PlGF) is a recently identified growth factor for endothelial cells (EC); PlGF strongly potentiates both the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. To uncover the molecular mechanisms underlying neoangiogenesis in human thyroid tumors, we have analysed VEGF and PlGF expression in a panel of thyroid carcinoma cell lines with different tumorigenic potential as well as in human primary thyroid tumors. We show that a high tumorigenic potential is associated with an elevated VEGF expression in human thyroid tumor cell lines. Furthermore, VEGF overexpression occurs in 5/5 highly malignant anaplastic carcinomas. Papillary and follicular carcinomas express intermediate levels of VEGF mRNA. In contrast, PlGF expression is severely down regulated in the majority of thyroid tumor cell lines and in tumors. Furthermore, we show that both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PlGF, contributes to thyroid tumor development.
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PMID:Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines. 747 81

The RET proto-oncogene, a transmembrane tyrosine kinase receptor, is involved in the development of at least five different disease phenotypes. RET is activated through somatic rearrangements in a number of cases of papillary thyroid carcinoma while germ-line point mutations are associated with three inherited cancer syndromes MEN 2A, MEN 2B and FMTC. Moreover, point mutations or heterozygous deletions of RET are found in the dominant form of Hirschsprung disease or congenital colonic aganglionosis. We cloned the entire RET genomic sequence in a contig of cosmids encompassing 150 kb, from the CA repeat sTCL-2 to the region upstream the RET promoter, and established the position of the 20 exons of the RET gene with respect to a detailed restriction map based on eight endonucleases. A new highly polymorphic CA repeat sequence was identified within intron 5 of RET (RET-INT5). Finally the orientation of RET on chromosome 10q11.2 made it possible to orientate three other genes rearranged with RET in papillary thyroid carcinomas, namely H4/D10S170 on 10q21, R1 alpha on 17q23 and RFG2/Ele1 on 10q11.2.
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PMID:The physical map of the human RET proto-oncogene. 747 1

A recent in vitro study has suggested that overexpression of ERBB2 may mediate breast tumour progression and metastasis by inhibiting the transcription of the E-cadherin (E-CD) gene. To test this hypothesis in human breast cancer in vivo, we studied the relationship between the expression of both molecules in 247 breast carcinomas immunohistochemically. Five ductal carcinomas in situ overexpressed ERBB2 and showed preserved E-CD expression. Forty-four of 226 infiltrating ductal carcinomas (19.47%) showed ERBB2 overexpression, and a statistically significant relationship was found between ERBB2 overexpression and high histological grade. E-CD expression was preserved in 111 cases (49.1%) and correlated with the histological grade. However, no significant relationship was found between ERBB2 and E-CD expression. None of the 16 infiltrating lobular carcinomas expressed ERBB2 or E-CD. These observations in different histological types of breast carcinoma strongly argue against a role for ERBB2 as a transcriptional regulator of E-CD expression in most human breast carcinomas in vivo.
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PMID:Relationship between ERBB2 and E-cadherin expression in human breast cancer. 749 94

In an attempt to verify the nature of amplification events at band q13 on chromosome 11 we surveyed the amplification status of ten molecular markers specific for this region (GSTP, SEA, D11S97, D11S146, BCLI, PRADI/CCNDI, HST/FGF4, INT2/FGF3, EMSI, and DIIS833E) in a panel of 389 primary breast carcinoma DNA samples. Eighty-eight tumors (23%) showed at least one of these markers amplified, but in a majority of the cases amplification encompassed more than one of the tested loci. Our data confirm that amplicons at 11q13 can cover large portions of DNA and are consistent with the existence of several cores of amplification. One important core seems to be, as previously described, centered around PRADI/CCNDI; 57 tumors (14.7%) showed amplification at PRADI/CCNDI either alone (one tumor) or along with amplification of BCLI or INT2/FGF3. The level of amplification of PRADI/CCNDI sometimes exceeded that of surrounding markers. Three additional amplification events occurring independently of amplification of PRADI/CCNDI were also detected. Centromeric to BCLI, probes to DIIS97, and DIIS146 detected amplification in 60 tumors (15.4%) and were often the only amplified markers. Telomeric to INT2/FGF3, DIIS833E was found amplified alone in ten tumors, and it was the most amplified marker in another six cases. At a shorter distance of INT2/FGF3, EMSI was the only amplified marker in two tumors, with a level of amplification that could exceed that of PRADI/CCNDI and DIIS833E. Our data thus suggest the existence of four independent amplified regions within band 11q13 in breast cancer.
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PMID:Patterns of DNA amplification at band q13 of chromosome 11 in human breast cancer. 750 99

Activation of the RET protooncogene tyrosine kinase (tk) by fusion with other genes is a frequent finding in papillary thyroid carcinoma. The tk domain of proto-RET can be fused either with the D10S170 gene generating the RET/PTC1 transforming sequence or with sequences belonging to the gene encoding the regulatory subunit RIA of c-AMP-dependent protein kinase A, thus forming the RET/PTC2 oncogene. We have previously shown that an inversion of chromosome 10, inv(10)(q11.2q21), is responsible for the generation of the RET/PTC1. Here we report that a chromosomal translocation, t(10;17)(q11.2;q23), juxta-poses the tk domain of the RET protooncogene, which resides on chromosome 10, to a 5' portion of the RIA gene on chromosome 17, leading to the formation of the chimeric transforming gene RET/PTC2. The finding of the transforming protein in primary tumor cell extracts supports the conclusion that RET/PTC2 activation plays a role in papillary thyroid tumorigenesis.
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PMID:A t(10;17) translocation creates the RET/PTC2 chimeric transforming sequence in papillary thyroid carcinoma. 751 46

The prostatic growth factors require a membrane specific receptor to which they must bind in order to carry out their biological activities correctly. The aim of this study was to isolate and quantify the epidermal growth factor receptor in prostatic tissue and indirectly determine the growth factors acting on it (EGF, TGF alpha, PDGF, NGF, IGF). From September, 1992 to June, 1993, we studied 55 patients. These were divided into two groups: the first group comprised 49 patients with benign prostatic hyperplasia (BPH) and 6 patients with prostatic carcinoma comprised the second group. Samples of the prostate were obtained following suprapubic (12 cases), TUR (38 cases), radical prostatectomy (1 case) and transrectal biopsy (4 cases). The EGFR was determined by radioimmunoassay (EGFR-RIA, Vienna Lab, Labordiagnostica GmbH). For the overall group of patients, we obtained mean EGFR values of 6.36 +/- 0.59 fmol/mg of protein and a positivity of 96.36% and 100% for BPH and malignant proliferative processes, respectively. The foregoing data show that EGFR was isolated from the tissue we analyzed and has an evident role in the regulation of prostate growth.
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PMID:[Involvement of epidermal growth factor receptor (EGFR) in the etiopathogenesis of prostatic proliferative processes]. 752 95

The Heregulin (HGL) gene, encoding a ligand for a member of the ERBB receptor family, is located at 8p12-p22, in or close to a region frequently amplified in breast carcinoma. Amplification of HGL was detected in three of 83 (3.6%) cases of breast tumors. No overexpression of the gene was observed in the amplified tumors. This and the low incidence of amplification suggest that HGL is not the key gene of the 8p12 amplification but may be used as a marker of large amplification units.
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PMID:The Heregulin gene can be included in the 8p12 amplification unit in human breast cancer. 752 49

Breast cancer can relapse both locally and at distant metastatic sites. The mechanism of local recurrence is unknown, but seems to be due not only to the number of residual cancer cells (inadequate irradiation or surgery), but also to their genetically determined malignant potential. To identify genetic alterations associated with local recurrence risk in breast carcinoma, we analyzed 28 local recurrences and 173 primary breast tumors for the ten most frequently altered genetic regions in breast carcinomas, i.e., loss of heterozygosity on chromosomal arms 1p, 3p, 7q, 11p, 17p, 17q, and 18q, and amplification of the MYC and ERBB2 protooncogenes and of genes in 11q13. Only INT2/FGF3 and CCNDI, located in 11q13, were more frequently amplified in local recurrences than in primary tumors (39% vs. 17%; P < 0.01). Moreover, recurrence-free survival was shorter when the 11q13 region was amplified. These results suggest that one or more genes located in 11q13 play an important role in local relapses of breast cancer.
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PMID:11q13 amplification in local recurrence of human primary breast cancer. 753 85

We have constructed, expressed, and purified a fusion protein, HAR-TX beta 2, consisting of heregulin-beta 2 fused to a binding-defective form of Pseudomonas exotoxin A, PE40. The fusion protein was found to induce receptor tyrosine phosphorylation in CEM cells transfected with HER4 alone or in combination with HER2 but not in cells transfected with HER2 or HER1 alone. The phosphorylation of receptor tyrosines was both dose-dependent and saturable in amounts similar to those shown to be active for native heregulin. HAR-TX beta 2 was specifically cytotoxic toward a variety of carcinoma cell lines in the ng/ml range. However, some tumor cell lines were found to be insensitive to the cytotoxic action of the fusion protein even at > 2 micrograms/ml. Relative amounts of HER4, HER3, and HER2 were determined on seven cell lines sensitive and four cell lines insensitive to HAR-TX beta 2. All lines that express HER4 were killed by HAR-TX beta 2, while none lacking HER4 were affected. HAR-TX beta 2 was able to bind to and signal via tyrosine phosphorylation in cell lines that co-express HER2 and HER3 in the absence of HER4 without inducing cytotoxicity. Thus HAR-TX beta 2 may prove to be a useful reagent for the targeting and elimination of HER4-positive tumor cells.
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PMID:HER4 expression correlates with cytotoxicity directed by a heregulin-toxin fusion protein. 753 74

The retinoid N-(hydroxyphenyl) retinamide (4-HPR) appears to be a promising tool for chemoprevention of breast carcinoma, and clinical trials to evaluate its effect are in progress. However, its action on tumor cells has remained largely undefined. We report here that 4-HPR induced apoptosis and/or differentiation in breast cancer cell lines, independent of hormone receptor status and retinoic acid receptor expression, although it was slightly more efficient in inhibiting proliferation of estrogen receptor-positive cells. 4-HPR up-modulated expression of several differentiation markers (class 1 HLA, laminin, and beta 1 integrin chain) and down-regulated expression of molecules associated with tumor progression, including the p185/HER2 oncoprotein, the epidermal growth factor receptor, and the M(r) 67,000 laminin receptor. These data suggest that 4-HPR could exert a beneficial effect by inhibiting cell proliferation and modulating breast tumor aggressiveness.
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PMID:Modulation of markers associated with tumor aggressiveness in human breast cancer cell lines by N-(4-hydroxyphenyl) retinamide. 754 8


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