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)

Fusion of tumorigenic HeLa cells with human skin fibroblasts results in chromosomally stable hybrids that are nontumorigenic and no longer express the HeLa tumor-associated marker intestinal alkaline phosphatase (IAP). Previous studies of spontaneous tumorigenic segregants from the nontumorigenic hybrids implicated the loss of one copy of human fibroblast chromosome 11 in the concomitant reexpression of tumorigenicity. In an attempt to identify genes involved in the control of tumorigenic expression, we performed differential display screening of nontumorigenic hybrid cells and tumorigenic segregants. Subsequent northern blot analyses reproducibly showed 17 differentially expressed genes, eight of which were expressed differentially in the nontumorigenic hybrids and nine of which were expressed differentially in the tumorigenic hybrids. The former were genes for 80K-L protein (a substrate of protein kinase C), AXL/UFO (a receptor tyrosine kinase), insulin-like growth factor binding protein 3, apolipoprotein AI regulatory protein, collagen type I alpha-2 chain, transforming growth factor-beta-induced gene product 3 (BIGH3), pregnancy-specific beta-1-glycoprotein, and fibroblast activation protein alpha. The latter nine genes were genes for serum/glucocorticoid-regulated kinase (SGK; a serine/threonine protein kinase), PTPCAAX1 (a tyrosine phosphatase), CXCR-4 (a G-protein-coupled membrane receptor), L-kynurenine hydrolase, beta-1, 4-galactosyltransferase, keratin 8, keratin 17, and H19 and a novel gene. The differential expression of these genes provided several interesting candidates for regulation of tumorigenic expression, including those involved in signal transduction and the extracellular matrix, cytoskeletal proteins, cell-surface enzyme, and the H19 gene.
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PMID:Differential gene expression in tumorigenic and nontumorigenic HeLa x normal human fibroblast hybrid cells. 1056 6

Malignant and normal human breast tissue were compared by evaluating two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) maps of frozen tissue samples. Image analyzing software was used to scan and process 34 gels. Eight (8/34) of these gels (4 malignant breast tumor samples, 4 normal tissue samples) were selected on the basis of gel and image quality to build a database to identify and measure the expression of a previously unidentified proteome. Growth factor receptor proteins (GFRs), including ERBB2 (HER2) and ERBB3 (HER3), were expressed in the malignant tissue samples. Growth factor receptor proteins were not expressed in the normal tissue. Also, expression of PS2-protein (pS2) was detected in neither malignant nor normal tissue. In benign breast samples a higher intensity of protein expression could be observed for maspin, desmoglein 3 and keratin 8 than in malignant samples. Other proteins expressed in malignant breast tissue include mitogen-activated protein kinase 3 (MK03), heat shock protein 27 kDa (HS27), growth factor receptor-bound protein (GRB2), cathepsin D, G1/S specific cyclin E1 (CGEI), glucose transporter type 5 (GTR5), and a number of as yet unidentified proteins.
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PMID:Comparative analysis of two-dimensional protein patterns in malignant and normal human breast tissue. 1142 69

Mammary small cell carcinoma (SmCC) is a very rare neoplasm with a poor prognosis compared with other invasive carcinomas. We studied the histological and immunohistochemical profiles of two cases of mammary SmCC, and compared them with those of five cases of carcinoma with endocrine features (CEF) and five cases of invasive ductal carcinoma (IDC), to elucidate the correct diagnosis of mammary SmCC. Immunohistochemical analysis was performed with antibodies against cytokeratins (CKAE1/AE3, CK34betaE12, CKCAM5.2, CK7, CK8, CK19, CK20), epithelial membrane antigen (EMA), vimentin, CD10, neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin A, S-100 protein, carcino-embryonic antigen (CEA), E-cadherin, N-cadherin, thyroid transcription factor-1 (TTF-1), p53, estrogen (ER), progesterone (PR), HER2/neu, bcl-2, synaptophysin, calcitonin and Leu7. SmCCs were diffusely and strongly positive for NCAM in comparison with CEFs and IDCs. SmCCs were negative for vimentin, whereas CEFs and IDCs were positive. Neuro-endocrine carcinomas, including SmCCs and CEFs, were diffusely and strongly positive for NSE, compared with IDCs. Moreover, neuroendocrine carcinomas were negative for CK34betaE12, CK20 and CD10, whereas IDCs were positive. Our study suggests that NCAM and vimentin are useful markers for the diagnosis of mammary SmCC. CK34betaE12, NSE, CD10, CK20 and chromogranin A appear to be useful for differentiating neuroendocrine carcinoma from IDCs.
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PMID:Comparative study of primary mammary small cell carcinoma, carcinoma with endocrine features and invasive ductal carcinoma. 1501 Aug 80

Not uncommonly, bile duct adenomas (BDAs) and hamartomas (BDHs) of the liver may be difficult to distinguish from metastatic well-differentiated ductal adenocarcinoma of the pancreas. However, this distinction is critical for proper staging and patient management. The primary purpose of this study was to determine if a panel of immunohistochemical stains can help distinguish BDA or BDH from metastatic pancreatic adenocarcinoma in the liver. Routinely processed tissue sections from 25 BDA, 10 BDH, 25 metastatic pancreatic adenocarcinomas to the liver and 6 cases each of metastatic colorectal, breast, and lung adenocarcinomas were immunohistochemically stained for CK7, CK8/CK18, CK19, CK20, p53, p63, TAG-72, monoclonal CEA (mCEA), polyclonal CEA (pCEA), HER-2/neu, AMACR (alpha-methylacyl-CoA racemase), Dpc4 (Smad4), and mesothelin. The slides were evaluated in a blinded fashion, and the results were compared between the benign and malignant lesions. Significantly more (P < 0.05) metastatic pancreatic adenocarcinomas were positive for CK20 (76%), p53 (60%), TAG-72 (88%), mCEA (92%), HER2/neu (40%), and mesothelin (64%) and showed loss of Dpc4 (44%), in comparison to BDA (CK20, 40%; p53, 0%; TAG-72, 0%; mCEA, 0%; HER2/neu, 12%; mesothelin, 0%; loss of Dpc4, 0%) or BDH (CK20, 10%; p53, 0%; TAG-72, 0%; mCEA, 10%; HER2/neu, 0%; mesothelin, 0%; loss of Dpc4, 0%). Of these antibodies, p53, TAG-72, mCEA, loss of Dpc4, and mesothelin had the highest specificity for pancreatic adenocarcinoma, with mCEA having the highest sensitivity (92%). No significant differences were observed in the degree of CK7, CK8/CK18, CK19, or pCEA expression between the three types of lesions. Although none of the BDA or BDH was positive for either p63 or AMACR, two of the metastatic pancreatic adenocarcinomas (8%) were positive for each of these peptides (P > 0.05). For nonpancreatic adenocarcinomas, mCEA showed a reasonably high sensitivity and 100% specificity in the differential diagnosis versus BDA. Immunohistochemical expression of p53, TAG-72, mCEA, mesothelin, and loss of Dpc4 can help distinguish metastatic pancreatic adenocarcinoma in the liver from BDA or BDH. Although p63 and AMACR are also specific for pancreatic adenocarcinoma, their low sensitivity limits their use in clinical practice.
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PMID:Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas from bile duct adenomas and hamartomas of the liver. 1572 8

We previously demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (AE-BS) 60 microg/ml has anti-proliferation activity and apoptosis effects to A549 human lung cancer cells. They can also cause tumor cell arrest in G2/M phase. To better understand its target protein in A549 cell, two-dimensional electrophoresis and liquid chromatography-tandem mass spectrometry were applied. The modification of keratin 8 was identified. By immunoblot, the expression of phosphorylated keratin 8 at Ser-73 was increased from 2.0 to 3.0-fold after AE-BS treatment 24 to 48 hr respectively as compared with untreated A549 control cells. Furthermore, the A549 cells were pretreated with 50 microM PD98059, a specific inhibitor of the upstream regulator of ERK1/2, or with the p38 kinase inhibitor 20 microM SB203580 or JNK inhibitor 20 microM SP600125 for 30 min, followed by 24 h of incubation with AE-BS, PD98059 can inhibit K8-Ser-73 hyperphosphorylation and prevented cell apoptosis which was induced by AE-BS significantly. By immunoblot, AE-BS also can induce ERK 1/2 phosphorylation. In conclusion, our data indicate that the AE-BS induced tumor apoptosis in A549 cells was related to ERK 1/2 activation. The molecular mechanism of hyperphosphorylation of K8 on Ser-73 was associated with ERK 1/2 activation rather than JNK and p38 kinase. The apoptosis induced by AE-BS may be related to K8 phosphorylation.
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PMID:Requirement for ERK activation in acetone extract identified from Bupleurum scorzonerifolium induced A549 tumor cell apoptosis and keratin 8 phosphorylation. 1576 73

Vimentin expression is a rather rare finding in invasive breast cancer, and is associated with high tumour invasiveness and chemoresistance. It is currently explained by two different biological theories: direct histogenetic derivation from myoepithelial cells, and epithelial-mesenchymal transition (EMT) reflecting the end-stage of breast cancer dedifferentiation. In this study we aimed to obtain further insights into the biological hallmarks of these vimentin-expressing breast cancers. We applied immunohistochemistry for vimentin and 15 other differentiation markers to a series of 364 invasive breast cancer cases, using tissue microarray technology. 7.7% of all tumours expressed vimentin. Almost all of these cases (19/21) were Grade 3 invasive ductal carcinomas, and the majority (13/21) of these were associated with a ductal in situ component. Vimentin expression was also seen in the respective in situ components and correlated positively with the expression of SMA, CD10, CK 5, p53, Mib-1 and EGFR. A negative correlation was seen for the expression of CK 8/18 and the oestrogen receptor. Vimentin-expressing carcinomas revealed a significantly higher average absolute number of cytogenetic alterations per case, but a significantly lower frequency of chromosome 16q losses compared to vimentin-negative cases. Our present results demonstrate that, despite analogies between vimentin-positive breast cancers and myoepithelial cells in their expression of differentiation-related proteins, neither myoepithelial histogenesis nor EMT can exclusively explain the biology of these distinct tumours. This is mainly supported by the significantly higher incidence of vimentin-expressing breast cancers compared to any other myoepithelial breast tumours and the fact that vimentin is already observed in ductal in situ components. We therefore propose the alternative hypothesis that vimentin-expressing breast carcinomas may derive from breast progenitor cells with bilinear (glandular and myoepithelial) differentiation potential.
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PMID:The origin of vimentin expression in invasive breast cancer: epithelial-mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential? 1590 73

Recent biological studies have classified breast carcinomas into HER2-overexpressing, estrogen receptor-positive/luminal, basal- and normal-like groups. According to this new biological classification, the objectives of our study were to assess the clinical, morphologic and immunophenotypic characteristics of adenoid cystic carcinoma of the breast in order to classify this subtype of breast carcinoma. A total of 18 cases of adenoid cystic carcinoma were identified from the Institut Curie files. Clinical information was available for 16 patients with a median follow-up of 6.5 years. Morphologically, all tumors were graded according to the system defined by Kleer and Oberman (histologic and nuclear grade). Immunophenotype was assessed with anti-ER, PR, HER-2, KIT, basal (CK5/6) and luminal cytokeratins (CK8/18) and p63 antibodies. One out of 18 tumors was nuclear grade 1 (16%), nine were nuclear grade 2 (50%) and eight were nuclear grade 3 (44%). All cases were estrogen receptor, progesterone receptor and HER-2 negative. Epithelial cells were strongly positive around glandular lumina with one or both cytokeratins, identifying the coexistence of CK5/6+ cells, CK5/6 and CK8/18+ cells, CK8/18+ cells and p63+ cells. All cases (100%) were also KIT positive. In all, 15 patients were treated by surgery. Nine of them received adjuvant radiotherapy. Follow-up was available for 16 patients. In all, 14 patients were alive. Two of them, initially treated by surgery only, presented a local recurrence. Two patients died (one of them treated by radiation therapy only died from her disease). Our study shows that adenoid cystic carcinoma of the breast is a special, estrogen receptor, progesterone receptor, HER-2 negative and highly KIT-positive, basal-like breast carcinoma, associated with an excellent prognosis. This highly specific immunophenotype could be useful to differentiate adenoid cystic carcinoma of the breast from other subtypes of breast carcinoma such as cribriform carcinoma.
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PMID:KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome. 1625 15

Immunohistochemistry is widely used for pathological diagnosis of breast lesions. Other than hormone receptors and HER2/neu analysis for primary breast carcinomas, several markers may be useful for differential diagnoses, although in limited situations. To decide the malignant potential of intraductal proliferative lesions, analysis for the staining pattern of cytokeratins may be a good reference. Most ductal carcinoma in situ cases are diffusely positive for luminal cell markers (CK8, CK18, CK19), but negative for basal cell markers (CK5/6 and CK14). However, usual ductal hyperplasia may show the mosaic staining patterns for any of these markers, which may indicate a heterogeneous cell population in benign lesions. Myoepithelial markers (alpha-SMA, myosin, calponin, p63, CD10) are almost consistently positive for benign papillomas but they do not completely distinguish intraductal papillary carcinomas. Preservation of myoepithelial layer is the diagnostic key when looking at benign sclerosing lesions, including carcinoma with pseudoinvasive structures. E-cadherin is mostly positive for ductal carcinomas but negative for lobular carcinomas. Some of the lobular carcinomas are positive for 34betaE12, but they are consistently negative for CK5/6. Comparison with histopathological findings of hematoxylin and eosin is essential to make proper diagnosis in the individual case.
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PMID:New trends of immunohistochemistry for making differential diagnosis of breast lesions. 1657 8

We have previously reported that high grade and non-high grade ductal carcinoma in situ (DCIS) of the breast can be subdivided into 3 cell origin subtypes (luminal, basal/stem, and null), and that high grade DCIS is more frequently associated with basal/stem cell subtypes compared to non-high grade DCIS. Here we refine the relationships between these 3 subtypes and the expression patterns of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (ERFR) in 53 cases of non-high grade and 46 cases of high nuclear grade DCIS. Using a panel of antibodies to ER-alpha, PR, HER-2/neu, and EGFR, along with cytokeratin (CK) markers (CK5/6, CK8, CK14, CK17, and CK18), we found that all 3 cell origin subtypes can express ER-alpha and PR, and their expression is higher in non-high grade DCIS than in high grade DCIS; the expression of HER-2/neu is associated with luminal subtype only in non-high grade DCIS, but can be seen in all 3 subtypes in high grade DCIS; the expression of EGFR is low and is present only in luminal cell subtypes in both high and non-high grade DCIS. Basal/ stem cell and null cell subtypes occur in younger patients in non-high grade DCIS compared to high grade DCIS. In conclusion, the expression patterns of ER-alpha, PR, HER-2/neu, and EGFR are markedly different in different cell origin subtypes of both high grade and non-high grade DCIS, suggesting that cell origin subtypes as well as nuclear grade contribute to the biological and molecular heterogeneity of DCIS.
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PMID:Expression patterns of ER-alpha, PR, HER-2/neu, and EGFR in different cell origin subtypes of high grade and non-high grade ductal carcinoma in situ. 1668 8

All the preliminary observations on a lot of marker sets defining different stages in the tumor development are building a framework of work hypothesis which can be verified in characterising large pools of histological uniform rated paraffin probes. We developed a bootstrapping algorithm based on correlation measures to uncover regulatory patterns of immunohistochemical characterized tissue arrays with 550 invasive breast cancer cases. The algorithm is implemented in 'S' a computer language used to model mathematical solutions. Focussing on the Cytokeratins versus a set of prominent markers in breast cancer differentiation it will be obvious that markers which are known to appear in early (progenitor) forms conform to CK5/6 and CK14 while others associated with late stages conform to CK8/18 and CK19. Markers examined are among others EGFR, EMA, erb-B2, Vimentin, p53, ER and PR. The developed approach is an elegant and complete procedure to reveal the real regulatory patterns which are enclosed in a certain experimental design. The statistical significance of the results calculated by our algorithm is generally high and in the presented experimental design smaller than 0.6 * 10E-6.
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PMID:[Bootstrapping algorithm approach reveals inherent regulatory pattern in 550 invasive breast cancer cases: CK5/6/CK14 and CK8/18/CK19 builds an antagonistic set]. 1803 93


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