Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human breast tumor cell line BT-474 derived from an invasive ductal carcinoma was experimentally infected in vitro with a mouse mammary tumor virus from the TIII strain (RIII-MuMTV). The virus that replicated in the human cells was characterized as a mouse virus by immunofluorescence, electron microscopy and the presence of a specific RNA-directed DNA polymerase. The cells themselves were human as per the karyotype and isoenzyme migration patterns. It is concluded that human cells are susceptible to the mouse mammary tumor virus and can, eventually, support its replication.
 ...
PMID:A human breast tumor cell line (BT-474) that supports mouse mammary tumor virus replication. 9 35

Thrombospondin-1 (TSP1) is a Mr 450,000 extracellular matrix glycoprotein that modulates tumor growth, angiogenesis, and metastasis. Of the five structurally different TSPs described to date, only TSP2 is similar to TSP1 in terms of its molecular architecture, and TSP2 also modulates angiogenesis. Angiogenesis plays a relevant role in the biological aggressiveness of breast cancer, and TSP1 is present in the tumor stroma (termed desmoplasia) of invasive human breast ductal carcinoma not otherwise specified (NOS). The present study was designed to identify and quantify TSP1 and TSP2 mRNAs in normal, benign, and neoplastic human breast tissues using the reverse transcriptase PCR technique. We found that TSP2, like TSP1, was expressed in human breast tissues, and that TSP1 and TSP2 mRNA expression in invasive breast carcinoma NOS was significantly increased compared to that observed in normal and benign tissues. The expression of TSP1 and TSP2 in invasive breast ductal carcinoma NOS did not significantly correlate with any of the prognostic factors studied (tumor size, lymph node status, morphology, and hormone receptor status). However, when our study population was divided according to the quantity of tumor stroma, TSP1 (and possibly TSP2) mRNA expression and microvessel counts in desmoplastic-rich stroma of breast carcinoma NOS were significantly increased compared to those observed in desmoplastic-poor stromata.
 ...
PMID:Thrombospondin-1 and -2 messenger RNA expression in normal, benign, and neoplastic human breast tissues: correlation with prognostic factors, tumor angiogenesis, and fibroblastic desmoplasia. 901 63

Tenascin-C is a modular glycoprotein composed of domains of amino acid repeats. All forms of tenascin-C have eight constant fibronectin type III repeats, but additional fibronectin type III repeats can be spliced into a variable domain found between the fifth and sixth constant repeats. Four extra repeats, named A, B, C and D, have been examined previously. Here, we have used in situ hybridization to determine the tissue origins of the novel AD1 and AD2 repeats. In the embryonic-day-10 chicken embryo, transcripts encoding the AD2 repeat are limited to the tips of lung bronchioles and the base of feather buds. In contrast the AD1 hybridization signal was widespread. Quantitative in situ hybridization reveals AD1-containing transcripts represent up to 85% of the total tenascin-C mRNA in some tissues (developing bone), and are undetectable in others (e.g. radial glia). Avian and human tumor cell lines were examined for the expression of the AD1 repeat using the reverse transcriptase polymerase chain reaction (RT-PCR). Transcripts encoding six different tenascin-C splice variants incorporating the AD1 repeat were found in the fibrosarcoma cell line, QT6. Many human tumor cells, including malignant melanoma and ductal breast carcinoma, were positive for AD1 tenascin-C expression. In addition, we found evidence of AD1 tenascin-C expression in samples of excised human tumors. Our results show that a novel variant may be a major part of the tenascin-C of the embryonic extracellular matrix, and may also be found in the stroma surrounding some human tumors.
 ...
PMID:The expression of tenascin-C with the AD1 variable repeat in embryonic tissues, cell lines and tumors in various vertebrate species. 940 2

Intraductal papillary neoplasia of the liver (IPNL) frequently presents gastrointestinal metaplasia with aberrant expression of MUC2 and MUC5AC and oversecretion of mucin into the ductal lumen. In this study, the involvement of CDX2, a homeodomain protein involved in the regulation of intestinal development and differentiation, in the expression of MUC2 was examined in mucinous intrahepatic cholangiocarcinoma (ICC) (n=7) and IPNL with hepatolithiasis (n=19) with comparison to conventional ICC (n=11), and intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas (n=9 and 11, respectively). A total of 33 cases of hepatolithiasis, extrahepatic biliary obstruction and normal livers were used as the control. Immunohistochemically, both MUC2 and MUC5AC were frequently expressed in mucinous ICC and IPNL, while expression of MUC2 was not seen in conventional ICC. The nuclear expression of CDX2 was closely associated with the expression of MUC2 in mucinous ICC and IPNL. This intimate association of MUC2 and CDX2 was confirmed by double immunostaining. The cytoplasmic CDX2 expression was frequent in the mucinous and the conventional ICC and pancreatic carcinoma, irrespective of MUC2 and MUC5AC expression. CDX2 mRNA was detected in neoplastic cells showing cytoplasmic as well as nuclear expression of CDX2 by reverse transcriptase-polymerase chain reaction. One IPMT expressed MUC2 associated with nuclear CDX2 expression, while the other IPMT and conventional pancreatic carcinoma expressed MUC5AC only. Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous ICC and IPNL associated with hepatolithiasia, suggesting its role in intestinal differentiation and its association with carcinogenesis in these tumors.
 ...
PMID:Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis. 1504 36

Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.
 ...
PMID:Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion. 1523 95

A common feature of human breast oncogenesis is cell cycle deregulation. The expression of cyclins D1 and D3 was examined during estradiol-17beta (E(2))-induced mammary tumorigenesis in female August Copenhagen Irish (ACI) rats. Low serum E(2) levels ( approximately 60-120 pg/ml) were sufficient to induce mammary gland tumors (MGTs) that remarkably resemble human ductal breast cancer (BC) at the histopathologic and molecular levels. Western blot analysis of the E(2)-induced MGTs revealed a marked rise in cyclins D1 (24-fold), D3 (9-fold) and cdk4 (3-fold) expression compared with age-matched untreated controls. Small focal dysplasias with large, pale staining nuclei were commonly seen at 3-3.6 months, large focal dysplasias, including atypical ductal hyperplasia at 3.6-4.3 months, ductal carcinoma in-situ (DCISs) at 4.3-5.0 months, and 100% incidence of invasive ductal BC/frank tumors at 5-6 months were detected after E(2) treatment. Immunohistochemical analysis of serial sections of focal dysplasias, DCISs and invasive ductal carcinomas showed overexpression of cyclins D1, D3, estrogen receptor-alpha (ERalpha) and progesterone receptor (PR). However, cyclin D3 expression, unlike D1, was confined essentially to early pre-malignant lesions (focal dysplasias and DCISs) and primary MGTs with <1-5% of resting and normal hyperplastic breast cells staining positive. The kinase activity for cyclins D1 and D3, using retinoblastoma (Rb) as a substrate, in E(2)-induced MGTs and their binding to cdk4 was significantly elevated. Semi-quantitative reverse transcriptase PCR analysis of the E(2)-induced MGTs exhibited increased expression of cyclins D1 (2.9-fold) and D3 (1.4-fold) mRNA, indicating that their elevated protein expression was due in part to an increase in mRNA transcription. However, when analyzed by quantitative real-time Q-PCR, these genes were not amplified. These data indicate that in female ACI rat mammary glands, E(2)-induced pre-malignant lesions differentially and selectively express cyclins D1 and D3, thus contributing to a distinct growth advantage of these pre-neoplasias relative to E(2)-elicited normal hyperplasia.
 ...
PMID:Overexpression of cyclins D1 and D3 during estrogen-induced breast oncogenesis in female ACI rats. 1631 Dec 45

Secretory carcinomas (SBC) are characterized by their characteristic histomorphology and more favorable prognosis compared to invasive ductal carcinoma of usual type (IDC). On this basis, 13 SBCs are evaluated by molecular and immunohistochemical (IH) methods. 13 SBCs and 4 IDCs were analyzed for ETV6-NTRK3 gene fusion by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Fluorescence in situ Hybridization (FISH). 8 of 13 microdissected SBCs with evaluable DNA were evaluated for genetic alterations (GA) by comparative genomic hybridization (CGH). IH included estrogen-receptor (ER), progesterone-receptor (PR), Her-2/neu and Ki-67 (MIB-1) in all 13 cases. Molecular and immunohistochemical results in SBCs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. 12 of 13 (92 %) SBC cases, but not IDCs expressed the ETV6-NTRK3 fusion gene which encodes a chimeric tyrosine kinase. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary epithelial cells resulted in transformed cells that readily formed epithelial tumors in nude mice. CGH revealed an average of 2.0 GAs (range 0-6), including recurrent gains of chromosome 8q and 1q and losses of 22q. Four SBCs were positive for ER and 2 were positive for PR. The mean MIB-1-labeling index was 11.4% (range: <1-34%). Her-2/ neu protein overexpression was detected in 1 case (score 3+). Compared to previous findings in IDCs, SBCs are characterized by the recurrent expression of ETV6-NTRK3 fusion gene, a relatively low number of GAs, low proliferative rate, infrequent Her-2/ neu protein overexpression and a lower rate of steroid hormone receptor expression. These results support the hypothesis that SBCs have immunohistochemical and genetic features that specifically distinguish them from IDCs.
 ...
PMID:Secretory carcinoma of the breast: a genetically defined carcinoma entity. 1688 13

Hypoxia and acidosis are microenvironmental selection forces during somatic evolution in breast carcinogenesis. The effect of cobalt chloride (CoCl(2))-induced hypoxia on the expression of hypoxia-inducible factor (HIF)-1alpha, glucose transporter 1 (GLUT1), and carbonic anhydrase IX (CAIX) was assessed in breast cancer cells derived from primary sites (HCC1395 and HCC1937) and metastatic sites (MCF-7 and MDA-MB-231) by reverse transcriptase-polymerase chain reaction and immunoblotting. We analyzed these proteins' expression in tissue samples from normal breast tissue, usual ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) using immunohistochemistry. CAIX mRNA was expressed constitutively in MDA-MB-231 cells but not in the other three cell lines. CAIX mRNA expression was increased after CoCl(2)-induced hypoxia in all four breast cancer cell lines. The expression of HIF-1alpha and GLUT1 proteins was increased after CoCl(2)-induced hypoxia in all breast cancer cell lines tested. Hypoxia significantly increased CAIX protein expression in primary cancer cells but not in metastatic ones. HIF-1alpha was not expressed in benign breast tissue, whereas it was significantly expressed in DH, ADH, DCIS, and IDC (p < 0.001). GLUT1 and CAIX were expressed only in DCIS (56.8% and 25.0%) and IDC (44.1% and 30.5%), with higher expression in high grade DCIS than low/intermediate grade DCIS (79.2% vs. 30.0%, p = 0.001 and 37.5% vs. 10.0%, p = 0.036, respectively). High CAIX expression was significantly associated with poor histological grade of IDC (p = 0.005). During breast carcinogenesis, the role of HIF-1alpha changes from response to proliferation to tumor progression. GLUT1 expression (glycolytic phenotype) and CAIX expression (acid-resistant phenotype) may result in a powerful adaptive advantage and represent an aggressive phenotype.
 ...
PMID:Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1alpha, GLUT1, and CAIX. 2052 21