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)

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

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

We have previously reported that a decreased expression level of ICAM-1 in cancer cells frequently led to the development of lymph node metastasis, and suggested that ICAM-1 gene transfection may inhibit lymph node metastasis. In the present study, we investigated whether ICAM-1 gene therapy for the peritoneal metastasis of gastric carcinoma is useful as a new immuno-gene therapy. ICAM-1 gene was transfected into a gastric cancer cell line, OCUM-2MD3 (2MD3), which has a high metastatic ability to the peritoneum. A transfectant cancer cell line, 2MD3/ICAM-1, had high ICAM-1 expression on the cell surface. The adhesion and cytotoxicity abilities of peripheral blood mononuclear cells were significantly increased against 2MD3/ICAM-1 cells in comparison with 2MD3 cells. Mice inoculated with 2MD3/ICAM-1 cells in the peritoneal cavity had a significantly better survival rate than those inoculated with 2MD3 cells (log-rank test, p<0.05). Histologic findings revealed that more mononuclear cells existed around the metastatic nodules in 2MD3/ICAM-1. Although gastric carcinoma frequently causes peritoneal metastasis, no useful therapy for the metastasis of gastric carcinoma has been developed. These findings revealed that ICAM-1 gene transfection to cancer cells could be a useful immuno-gene therapy for the peritoneal metastasis of gastric carcinoma.
Int J Mol Med 2002 Nov
PMID:Lipid-mediated gene transfection of intercellular adhesion molecule-1 suppresses the peritoneal metastasis of gastric carcinoma. 1237 2

We report the isolation and functional characterization of the gene encoding MGr1-Ag, a multidrug-resistance-associated protein. A lambdagt11 cDNA library derived from colorectal carcinoma SW480 cells was screened with monoclonal antibody MGr1. DNA homology analysis of 22 positive clones (designated R1-R22) suggested human 37-kDa laminin receptor precursor (37LRP, R7/R9/R15/R16/R19/R20) and a novel gene (R22) as candidate genes encoding MGr1-Ag. Western blot analysis showed that anti-R20 serum reacted with a unique protein band that was consistent with MGr1-Ag, while anti-R22 serum could not react with MGr1-Ag. The coding gene for MGr1-Ag was amplified using reverse transcription-PCR. Sequence analysis revealed that the MGr1-Ag and 37LRP genes shared the same coding sequence. An in vitro drug sensitivity assay indicated that down-regulation of 37LRP by an antisense technique could significantly enhance the cytotoxicity of anticancer drugs to gastric cancer cells. Thus we draw the conclusion that MGr1-Ag is identical to 37LRP.
Cell Mol Life Sci 2002 Sep
PMID:Multidrug-resistance-associated protein MGr1-Ag is identical to the human 37-kDa laminin receptor precursor. 1244 Jul 78

Protodioscin (PD) was purified from fenugreek (Trigonella foenumgraecum L.) and identified by Mass, and 1H- and 13C-NMR. The effects of PD on cell viability in human leukemia HL-60 and human stomach cancer KATO III cells were investigated. PD displayed strong growth inhibitory effect against HL-60 cells, but weak growth inhibitory effect on KATO III cells. Morphological change showing apoptotic bodies was observed in the HL-60 cells treated with PD, but not in KATO III cells treated with PD. Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 75.2, 96.3, and 100% after a 3-day treatment with 2.5, 5, and 10 microM PD, respectively. The fragmentation by PD of DNA to oligonucleosomal-sized fragments, that is a characteristic of apoptosis, was observed to be both concentration- and time-dependent in the HL-60 cells. These findings suggest that growth inhibition by PD of HL-60 cells results from the induction of apoptosis by this compound in HL-60 cells.
Int J Mol Med 2003 Jan
PMID:Protodioscin isolated from fenugreek (Trigonella foenumgraecum L.) induces cell death and morphological change indicative of apoptosis in leukemic cell line H-60, but not in gastric cancer cell line KATO III. 1246 12

Peritoneal dissemination is one of the most common modes of gastric cancer recurrence even after curative resection. Cytological examination of peritoneal lavage fluid is useful for detection of free cancer cells in the peritoneal cavity. However, some patients with negative cytological findings have peritoneal metastases of their gastric cancer. The purpose of the present study was to investigate the incidence and clinical significance of metastases harbored in the peritoneal cavity of patients with gastric carcinoma. Peritoneal lavage fluid was collected from the left subphrenic or Douglas cavities of 136 gastric cancer patients without macroscopic peritoneal metastases and 31 patients with benign disease. Peritoneal lavage fluid was examined by both conventional cytological examination (Papanicolaou and Giemsa staining), and carcinoembryonic antigen (CEA)-specific reverse transcription-polymerase chain reaction (RT-PCR). Among 136 gastric cancer patients, 5 patients (3.6%) were positive for free cancer cells by cytological examination and 30 (22.1%) were positive by RT-PCR. A difference in positivity between the left subphrenic and Douglas cavity was found in 18 patients by RT-PCR. The frequency of RT-PCR results increased according to lymph node metastases, lymphatic invasion, depth of tumor invasion and stage grouping. The incidence of peritoneal recurrence was significantly higher in patients with positivity than those with negativity by RT-PCR (p<0.0001). Among cytologically negative patients, survival was significantly shorter in patients with positive than in those with negative CEA-mRNA expression (p<0.0001). The technique of RT-PCR was more sensitive than cytological examination in the detection of cancer cells and prediction of peritoneal recurrence. Adjuvant therapy may be advisable for the gastric cancer patients with positive findings of peritoneal lavage by RT-PCR.
Int J Mol Med 2003 Jan
PMID:Clinical significance of CEA-mRNA expression in peritoneal lavage fluid from patients with gastric cancer. 1246 23

Peroxiredoxin II (Prx II) is known not only to protect cells from oxidative damage caused by hydrogen peroxide (H202), but also to endow cancer cells with resistance to both H202 and cisplatin and to grant them radioresistance. In this study, we examined whether Prx II antisense could enhance cisplatin-induced cell death. When gastric cancer cells were transfected with various concentrations of Prx II antisense plasmid, pPrxII/AS, and then treated with the same concentrations of cisplatin, Prx II antisense enhanced cisplatin-induced cell death. The combination index (CI) at all doses of the combination was below 1, indicating that Prx II antisense sensitized cisplatin-induced cell death. This synergism was also observed in the cells transfected with a Prx II antisense oligomer. Our present results, therefore, suggest that Prx II antisense would be a very good sensitizer for cisplatin, and that Prx II as a target for chemosensitizers constitutes a promising avenue for future research.
Exp Mol Med 2002 Sep 30
PMID:Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death. 1251 92

Camptothecin, a topoisomerase I inhibitor, is a well-known anticancer drug. However, its mechanism has not been well studied in human gastric cancer cell lines. Camptothecin induced apoptotic cell death in human gastric cancer cell line AGS. Z-VAD-fmk, pan-caspase inhibitor, blocked apoptotic phenotypes induced by camptothecin suggesting that caspases are involved in camptothecin-induced cell death. An inhibitor of caspase-6 or -8 or -9 did not prevent cell death by camptothecin. Various protease inhibitors failed to prevent camptothecin-induced cell death. These results suggest that only few caspases are involved in camptothecin-induced cell death. Camptothecin induced phosphorylation of ERK1/2, JNK, and p38 MAPK, in a dose and time-dependent manner in AGS. Z-VAD-fmk did not affect MAPK signaling induced by camptothecin suggesting that caspase signaling occurs downstream of MAPK signaling. Blocking of p38 MAPK, but not ERK1/2, resulted in partial inhibition of cell death and PARP cleavage by camptothecin in AGS. Taken together, MAPK signaling is associated with apoptotic cell death by camptothecin.
Mol Cells 2002 Dec 31
PMID:MAPK signaling is involved in camptothecin-induced cell death. 1252 Dec 96

The existence of occult metastasis in peripheral blood has been reported in various tumors. However, in gastric cancer (GC), this metastasis has not been well analyzed. In the present study, to identify circulating cancer cells in patients with GC, peripheral blood samples from GC patients were investigated. Total RNA was extracted from 1.5 ml peripheral blood from 55 patients with GC, from 34 non-cancer patients, and from 10 healthy volunteers. Carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and 20 (CK20) messenger RNA (mRNA) were used as probes to detect GC cells in the blood samples using real-time reverse transcriptase polymerase chain reaction (RT-PCR). CEA and CK19 mRNA expression were not detected in the 40 healthy volunteers and non-cancer patients, while 2 of the 40 showed CK20 mRNA expression. In 55 patients with GC, CK19 mRNA was not detected and CEA mRNA was detected in only one case (1.8%) with stage IV. While CK20 mRNA expression was observed in 15 cases (27.3%) and even in stage I, 8 of 24 (33.3%) showed CK20 mRNA expression. Thus, the specificity of CK20 marker may be low. Even though the sensitivity of CEA marker is low, CEA may be a more reliable marker than cytokeratins for detection of cancer cells in GC patient's peripheral blood.
Int J Mol Med 2003 Feb
PMID:Detection of cancer cells in the peripheral blood of gastric cancer patients. 1252 81


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