Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During Drosophila hindgut development, bowl, caudal/CDX, brachyenteron/Brachyury/TBX, fork head/FOX, drumstick, lines, and wingless/WNT play important roles. Drosophila bowl gene is homologous to Drosophila odd-skipped (odd) gene and odd-skipped related gene (sob). Here, human OSR1, related to Drosophila odd, was isolated using bioinformatics and cDNA-PCR. OSR1 was found to encode 266 amino-acid protein with three C2H2-type zinc fingers, a tyrosine phosphorylation site (Tyr 203), and several putative PXXP SH3 binding motifs. Three zinc fingers and a tyrosine phosphorylation site were conserved among human OSR1, OSR2, Drosophila odd, sob, and bowl. OSR1 showed 63.6% total amino-acid identity with OSR2. OSR1 gene consisting of three exons was located on human chromosome 2p24. OSR1 mRNA of 2.3-kb in size was detected in adult colon, small intestine, prostate, testis, and fetal lung. OSR1 mRNA was significantly up-regulated in a pancreatic cancer cell line MIA PaCa-2, and was weakly expressed in gastric cancer cell lines OKAJIMA, MKN45, pancreatic cancer cell lines PANC-1, BxPC-3, AsPC-1, PSN-1, Hs766T, and esophageal cancer cell line TE10. Among 10 cases of primary gastric cancer, OSR1 mRNA was up-regulated in 5 cases, and was down-regulated in 2 cases. This is the first report on molecular cloning and characterization of human OSR1.
Int J Mol Med 2002 Aug
PMID:Molecular cloning and characterization of OSR1 on human chromosome 2p24. 1211 63

SOX proteins are a family of transcription factors with high-mobility-group DNA-binding domain (HMG box) homologous to SRY, which play key roles in embryogenesis. Xenopus Sox17alpha, Sox17beta, Sox3 and mouse Sox7 are reported to be negative regulators of the WNT-beta-catenin-TCF signaling pathway. SOX7, SOX17, and SOX18 constitute a subfamily among the SOX gene family. Here, expression of SOX18 mRNA was investigated using Northern blot analysis, RNA dot blot analysis, and cDNA-PCR. SOX18 mRNA was significantly highly expressed in ventricles and inter-ventricular septum of adult heart among various normal human tissues. SOX18 mRNA was relatively highly expressed in stomach and jejunum in the gastrointestinal tract. SOX18 mRNA was relatively highly expressed in TMK1 and MKN45 among 7 gastric cancer cell lines. SOX18 mRNA was expressed in all out of 7 pancreatic cancer cell lines, and was relatively highly expressed in PANC-1, Hs700T, Hs766T and MIA PaCa-2. Expression level of SOX18 mRNA in MCF-7 cells (breast cancer) was not affected by beta-estradiol. SOX18 mRNA was expressed in all out of 5 embryonal tumor cell lines, and was relatively highly expressed in NT2 with the potential to differentiate into neuronal cells. Expression level of SOX18 mRNA in NT2 cells was down-regulated by all-trans retinoic acid. This is the first report on comprehensive expression analyses of SOX18 mRNA in normal human tissues and tumors.
Int J Mol Med 2002 Sep
PMID:Expression of human SOX18 in normal tissues and tumors. 1216 11

WNT signaling pathway plays key roles in carcinogenesis and embryogenesis, and WNT signaling molecules are potent targets for diagnosis, prevention and treatment of cancer as well as for regenerative medicine or tissue engineering. We have so far cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14 and WNT14B/WNT15 using bioinformatics and cDNA-PCR. We have also reported frequent up-regulation of WNT2 and WNT5A in primary gastric cancer, which is probably due to cancer-stromal interaction. Here, expression and regulation of WNT5A and WNT5B in human cancer were investigated. WNT5A was relatively highly expressed in TE6 and TE10 among 12 esophageal cancer cell lines, and WNT5B was expressed in the majority of esophageal cancer cell lines. Among 7 pancreatic cancer cell lines, WNT5A was up-regulated in Hs700T, and WNT5B in PANC-1. WNT5A, but not WNT5B, was up-regulated by TNFalpha in MKN45 cells derived from gastric cancer. WNT5B, but not WNT5A, was up-regulated by beta-estradiol in MCF-7 cells derived from breast cancer. WNT5A and WNT5B were expressed together in 5 embryonal tumor cell lines, and were slightly down-regulated by all-trans retinoic acid in NT2 cells. Up-regulation of WNT5A and WNT5B in several types of human cancer expressing FZD5 might lead to more malignant phenotype through activation of the beta-catenin - TCF pathway.
Int J Mol Med 2002 Sep
PMID:Expression and regulation of WNT5A and WNT5B in human cancer: up-regulation of WNT5A by TNFalpha in MKN45 cells and up-regulation of WNT5B by beta-estradiol in MCF-7 cells. 1216 12

Here we report the expression of major pyrimidine metabolising enzymes in pancreatic cancer cell lines, chronic pancreatitis tissue and human pancreatic cancer and the in vitro uptake of 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT). The expression of pyrimidine metabolising enzymes was evaluated with real-time PCR, Western blot and immunostaining. Thymidine kinase 1 (TK-1) activity was measured with a fluorocytometric assay. The cellular uptake and intracellular metabolism of [(18)F]FLT were evaluated in pancreatic lobules and in transformed cancer cell lines. TK-1 and thymidine synthetase mRNA were increased in six pancreatic cancer cell lines, while mRNA levels of thymidine kinase 2 and deoxycytidine kinase were down-regulated. High TK-1 activity was confirmed in all cell lines. Furthermore, TK-1 was overexpressed in human pancreatic cancer as compared with normal pancreatic tissue and samples from patients with chronic pancreatitis. The cellular uptake of [(18)F]FLT was 18.4%+/-3.6% and 5.2%+/-1.4% of the applied radioactivity after 240 min in SW-979 and BxPc-3 cells, respectively, while uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) was only 0.6%+/-0.04% (SW-979) and 0.3%+/-0.13% (BxPc-3) after 240 min of incubation. In contrast, cellular uptake of [(18)F]FLT in isolated pancreatic lobules and growth-arrested HT1080 cells was lower as compared with the uptake of [(18)F]FDG and with the malignant pancreatic cancer cell lines. HPLC analysis of the perchloric acid-soluble cell fraction demonstrated the phosphorylation of [(18)F]FLT to the respective monophosphate in both cell lines. Furthermore, 0.8%+/-0.12% (BxPc-3) and 1.3%+/-0.38% (SW-979) of the applied radioactivity was detected in the perchloric acid-insoluble cell fraction, indicating the incorporation of [(18)F]FLT into the DNA. Our results demonstrate the cellular uptake, intracellular trapping and incorporation into the DNA of [(18)F]FLT in pancreatic cancer cells in vitro. TK-1, as the rate-limiting enzyme of [(18)F]FLT metabolism, is overexpressed in pancreatic cancer cell lines and in human pancreatic cancer. Thus, we propose [(18)F]FLT as a promising tracer for positron emission tomography that might overcome current limitations in the diagnosis of pancreatic cancer.
Eur J Nucl Med Mol Imaging 2002 Sep
PMID:Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) in pancreatic cancer cell lines. 1219 62

We found that 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted anchorage-independent growth but did not affect anchorage-dependent growth of MIA PaCa-2 human pancreatic carcinoma cells. TPA markedly activated mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase in an anchorage-independent manner. Two protein kinase C (PKC) isoforms, conventional PKC (cPKC) and novel PKC (nPKC), but not apical PKC, translocated from the cytosolic to the particulate fraction upon TPA treatment. To identify the PKC isoforms involved in the regulation of anchorage-independent growth, four PKC isoforms (alpha, delta, epsilon, and zeta) were forced to be expressed in MIA PaCa-2 cells with an adenovirus vector. Overexpression of nPKCdelta or nPKC epsilon activated MAPK and promoted anchorage-independent growth. Overexpression of cPKCalpha alone did not influence anchorage-independent growth but lowered the concentration of TPA that was required to enhance such growth. Expression of constitutively active MAPK kinase-1 (MEK1) also promoted anchorage-independent growth. Furthermore, PKC inhibitors or an MEK inhibitor completely suppressed both TPA-induced activation of MAPK and promotion of anchorage-independent growth, but a cPKC-selective inhibitor partially suppressed TPA-induced promotion of the growth. Based on these results, we suggest that MAPK activation, mediated by certain isoforms of PKC, plays a part in oncogenic growth of MIA PaCa-2 cells. In summary, our data indicated that specific inhibitors of the cPKC and nPKC signaling pathway might be selective anti-oncogenic growth agents for some types of human pancreatic cancer.
Mol Carcinog 2002 Aug
PMID:Enhancement of anchorage-independent growth of human pancreatic carcinoma MIA PaCa-2 cells by signaling from protein kinase C to mitogen-activated protein kinase. 1220 69

WNT signaling molecules, playing key roles in embryogenesis and carcinogenesis, are potent targets for regenerative medicine and clinical oncology. We have previously cloned and characterized the human orthologue of mouse proto-oncogene Wnt-10b using bioinformatics and cDNA-PCR. Human WNT10B is moderately expressed in MKN45 and MKN74 cells derived from human gastric cancer, and is up-regulated by tumor necrosis factor alpha (TNFalpha) in MKN45 cells. Here, expression and regulation of WNT10B in human cancer other than gastric cancer were investigated using cDNA-PCR. WNT10B mRNA was expressed in the majority of squamous cell carcinoma cell lines derived from esophageal cancer and cervical cancer. WNT10B mRNA was relatively highly expressed in TE3, TE6, TE10, TE11 (esophageal cancer), Hs700T (pancreatic cancer), SKG-IIIa, HeLa S3 (cervical cancer), and T-47D (breast cancer). Expression of WNT10B mRNA was up-regulated by beta-estradiol in MCF-7 cells expressing estrogen receptors. Expression of WNT10B mRNA was down-regulated by all-trans retinoic acid in NT2 cells with the potential of self renewal and neuronal differentiation. WNT10B might be implicated in self renewal of stem cells as well as in carcinogenesis through activation of the WNT - beta-catenin pathway.
Int J Mol Med 2002 Oct
PMID:Expression and regulation of WNT10B in human cancer: up-regulation of WNT10B in MCF-7 cells by beta-estradiol and down-regulation of WNT10B in NT2 cells by retinoic acid. 1223 2

Ninety percent of pancreatic cancers are classified as ductal adenocarcinoma and are not known to secrete pancreatic elastases of the acinar enzymes. In the present study, we investigated the expression and the changes in elastase genes expressed in pancreatic ductal carcinoma cells. The expression of elastase gene family molecules in pancreatic cancer cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) method using primer sets for conservative active domains among pancreatic elastases (PEs) and neutrophil elastase (NE). The PCR products were subcloned, sequenced and analyzed. Three distinct products were isolated in pancreatic carcinoma cells using the RT-PCR analyses. The sequencing revealed that one was identical with the PE IIIA isoform, and the remaining two were alternatively splicing forms of the PE IIIA. Four of five pancreatic cell lines expressed these splicing variants in a cell-dependent manner. The present study is the first report to demonstrate the expression of PE IIIA and its splicing variants in pancreatic carcinoma cells might represent another infiltrative feature of the pancreatic ductal cell carcinoma.
Int J Mol Med 2002 Nov
PMID:Pancreatic elastase IIIA and its variants are expressed in pancreatic carcinoma cells. 1237 99

Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain non-neuronal tumors. In pancreatic cancer NGF is overexpressed, and this overexpression is associated with increased perineural invasion. NGF has the potential to stimulate the growth of some pancreatic cancer cell lines, and this effect is mediated by the phosphorylation of tyrosine kinase receptor A and mitogen-activated protein kinase activation; it is dependent on the expression levels of tyrosine kinase receptor A and p75 receptors. To determine whether cancer cell-derived NGF can participate in the regulation of pancreatic cancer cell proliferation, PANC-1 human pancreatic cancer cells were stably transfected with a full-length human beta-NGF expression vector. In vitro and in vivo growth characteristics were analyzed by proliferation assays and invasion assays and in a nude mouse tumor model. Stable transfection of NGF in PANC-1 cells resulted in enhanced anchorage-dependent growth, with a decrease in doubling times of up to 50%, and in an approximately twofold increase in anchorage-independent cell growth and cell invasion. Furthermore, stably transfected PANC-1 cells showed enhanced tumorigenicity in nude mice. These results suggest that NGF has the capacity to act in a paracrine and/or an autocrine manner in pancreatic cancer and that it enhances cancer cell growth and invasion in vivo, thereby contributing to the aggressiveness and poor prognosis of this disease.
Mol Carcinog 2002 Nov
PMID:Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells. 1241 May 65

The gastrointestinal peptides gastrin and cholecystokinin (CCK) stimulate growth of human pancreatic cancer by a receptor-mediated process. The purpose of this study was to investigate the molecular and functional characteristics of the receptor associated with peptide-induced pancreatic cancer proliferation. Utilizing total RNA from human pancreatic cancer cells a cDNA was cloned and sequenced by RT-PCR and rapid amplification of cDNA ends methodology. The molecular characteristics of the receptor cDNA were studied by Northern analysis and protein structure by Western analysis. An antibody raised against the novel receptor was utilized to investigate the role of the CCK-C receptor on pancreatic cancer cellular growth using in vitro technology. A spliced variant of the CCK-B receptor was identified which differed from the CCK-B receptor by the presence of intron 4. Northern analysis showed a transcript size of 3.2 Kb for the receptor mRNA in the human pancreatic cancer specimens, and Western blotting revealed binding to a 49 kDa protein in pancreatic tumors. Immunoreactivity was found in pancreatic cancer cells and tumors with localization in the cytoplasm. Treatment of BxPC-3 human cancer cells with the antibody resulted in growth inhibition. These data reveal the presence of a unique CCK receptor in human pancreatic cancer that functions in growth and is not present in normal human pancreas. The term CCK-C or 'cancer' receptor has been proposed to signify the relationship of this receptor to neoplasia.
Int J Mol Med 2002 Dec
PMID:Characterization of the CCK-C (cancer) receptor in human pancreatic cancer. 1242 93

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-beta s (TGF-beta s). To determine whether TGF-beta s can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-beta receptor (sT beta RII) that blocks cellular responsiveness to TGF-beta 1. When injected s.c. in athymic mice, PANC-1 clones expressing sT beta RII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-beta s act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sT beta RII may ultimately have a therapeutic benefit in PDAC.
Mol Cancer Ther 2002 Jan
PMID:Soluble type II transforming growth factor-beta receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis. 1246 10


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