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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human osteosarcoma and fibrosarcoma cell lines were investigated for alterations in oncogenes, tumor suppressor genes, and growth factors, all of which have been implicated in tumor formation. Characterization of oncogenes that are involved in osteosarcoma formation, including the c-fos and c-myc oncogenes, indicated that all six osteosarcoma cell lines examined had 5- to 20-fold amplification of the c-myc oncogene, whereas neither of two fibrosarcoma cell lines c-myc amplification. Interestingly, only three of six osteosarcoma cell lines displayed altered c-myc immediate-early gene function. c-fos was found to be normal, both at the gene and functional levels, in all six osteosarcoma and both fibrosarcoma cell lines tested. Characterization of two tumor suppressor genes, p53 and RB1, that have been implicated in osteosarcoma formation indicated that p53 was altered in five of six osteosarcoma cell lines, whereas RB1 was altered in only two or six of these cell lines. Neither RB1 nor p53 was found to be altered in the fibrosarcoma cell lines tested. An additional transformation marker, autocrine growth-factor production, was observed in all six osteosarcoma cell lines and both fibrosarcoma cell lines examined. Finally, the differentiation state of the osteosarcoma cell lines was investigated via the bone differentiation markers alkaline phosphates and osteocalcin. Alkaline phosphatase activity was observed in four of six osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined. The alkaline phosphatase activity was a result of the expression of the bone/liver/kidney alkaline phosphatase isoform. High-level osteocalcin expression was observed in one of the osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined, although all cell lines demonstrated low-level osteocalcin expression. Together, these data demonstrate that relatively undifferentiated osteosarcomas commonly display c-myc amplification, p53 and RB1 mutation, and autocrine growth-factor production, all of which may play a role in osteosarcomagenesis.
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PMID:Analysis of oncogenes, tumor suppressor genes, autocrine growth-factor production, and differentiation state of human osteosarcoma cell lines. 757 9

Cholesteatoma epithelium is characterised by a keratinocyte dysregulation with a hyperproliferative growth and altered differentiation. In a variety of cells c-myc oncogene was found to be highly linked to the control of growth and differentiation. The expression of c-myc was studied in cholesteatoma epithelium using a monoclonal antibody directed against the 67 kD c-myc protein product and the alkaline phosphatase-anti-alkaline phosphatase-method. Furthermore for quantitative analysis we used a computer aided analysing system. In contrast to normal skin the keratinocytes of suprabasal layers showed a nuclear staining in cholesteatoma epithelium. The incidence of nuclear stainings of epithelial cells in cholesteatoma was significantly increased. Simultaneously, cytoplasmatic staining was observed in both skin and cholesteatoma with a stronger reactivity in the latter. Our findings suggest a participation of the c-myc oncogene in the reported dysregulation of cholesteatoma epithelium.
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PMID:[Immunohistochemical detection of c-myc proto-oncogene products in middle ear cholesteatoma]. 766 77

Expression of oncogene mRNA was investigated in 37 cases of hepatocellular carcinoma (HCC) surgically resected using in situ hybridization (ISH) technique. C-myc, c-Ha-ras and N-ras DNA probes labeled with biotin were used. The hybrids were detected by streptavidin-biotin alkaline phosphatase staining. Thirteen cases of liver cirrhosis and 16 cases of non-cirrhotic liver were also examined as controls. In HCC cases, c-myc mRNA was expressed in 15 of 37 cases. The c-myc positive cells were found unevenly both in cancerous regions and in non-cancerous regions, being mainly distributed near the cancer capsule. The hybrids were detected mostly in cytoplasm of cancer cells. In some cases, they were seen not only in the parenchymal cells but also in the non-parenchymal cells, such as histiocytes, Kupffer cells and fibroblastic cells. In control cases, c-myc mRNA was expressed in five of 13 cases of liver cirrhosis and in three of 16 cases of non-cirrhotic liver. The expression of c-Ha-ras mRNA could be detected in only three of 37 cases of HCC. These three cases were early staged HCC. The expression of N-ras mRNA was detected in five of 32 cases examined of HCC. These five cases were differentiated type HCC. These results suggest that c-myc gene might play an important role in evolution and progression of HCC, and that ras genes might play a role in hepatocarcinogenesis at early stage.
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PMID:[Study on the expression of oncogene mRNA in hepatocellular carcinoma using in situ hybridization technique]. 783 Jul 8

The polar-planar compound hexamethylene bisacetamide (HMBA) can inhibit HT29 colon carcinoma cell growth and induce a more benign phenotype, as defined by decreased anchorage-independent clonogenicity, loss of a cell surface malignancy marker, and decreased in vivo tumorigenicity. The principle aim of this study was to determine whether HMBA's effects on HT29 cell growth and biologic behavior correlate with effects on intestinal differentiation. Parallel studies were performed with sodium butyrate (NaBT), a potent inducer of intestinal differentiation. HT29 cell growth, proliferation, and markers of intestinal differentiation were assayed after short- and long-term treatment with HMBA, NaBT, or the combination. Both 5 mM HMBA and 5 mM NaBT were potent inhibitors of monolayer growth; in combination their effects were nearly additive. Inhibition of DNA synthesis was detectable within 6 h of treatment and was preceded by down-regulation of c-myc expression. Soft agar clonogenicity was also decreased by 90%, > 99%, and > 99% by HMBA, NaBT, and the combination, respectively. Despite these parallel effects on growth and in vitro markers of a benign phenotype, effects on intestinal differentiation were discordant. NaBT induced significant increases in membrane-associated alkaline phosphatase activity, cytosolic mucin content, PAS+/diastase-resistant cells, and ultrastructural evidence of intestinal cell differentiation. HMBA not only failed to induce markers of intestinal differentiation, but attenuated NaBT's effects when used in combination. These data suggest that growth and intestinal differentiation may be independently regulated in HT29 cells. They also suggest that expression of intestinal markers of differentiation is not a prerequisite for the acquisition of a more benign phenotype.
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PMID:Growth and intestinal differentiation are independently regulated in HT29 colon cancer cells. 792 96

The mode of action of the differentiation inducer 1-beta-D-arabinofuranosylcytosine (ara-C) is as yet unknown. We have analyzed the role of c-myc expression in ara-C-induced differentiation of K562 human erythroleukemia cells. Six hours after differentiation induction, c-myc expression is down-regulated transiently. This was followed by the onset of cell differentiation together with a final c-myc 'down-regulation' at 24 h after treatment. This regulation of expression may be caused by hypermethylation of c-myc DNA sequences, which we find to follow a similar pattern. We propose that the loss of c-myc expression might be a necessary prerequisite for ara-C-induced differentiation. This hypothesis was tested by transfecting a constitutive c-myc expression construct into K562 cells prior to ara-C treatment. By following the differentiation parameters cell morphology, benzidine staining (hemoglobin monitored), and alkaline phosphatase activity (presence of mature red blood cell antigen monitored) in cells expressing cotransfected LacZ marker gene, it was demonstrated that the introduction of the c-myc expression plasmid blocked ara-C-induced differentiation. We conclude that loss of c-myc expression mediated the differentiation found in ara-C-treated K562 cells.
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PMID:Essential role of c-myc in ara-C-induced differentiation of human erythroleukemia cells. 805 66

Selected G1 events associated with butyrate-induced differentiation were examined in HT-29 colon adenocarcinoma cells. [3H]Thymidine incorporation by HT-29 cells was decreased to 40% of control levels by treatment with 5 mM butyrate for 24 h, and cell numbers decreased to 21% of control levels after 48 h of treatment. Cells released from butyrate arrest entered S phase approximately 24 h after release, and serum-deprived HT-29 cells escaped growth inhibition if butyrate was added 8 h or more after serum restimulation. Northern analysis of RNA isolated from rapidly growing HT-29 cells showed a marked induction of alkaline phosphatase mRNA expression within 12 h of treatment with 5 mM butyrate. The appearance of alkaline phosphatase mRNA was temporally associated with a 5-fold increase in expression of transforming growth factor beta 1 (TGF-beta 1) mRNA. Expression of the nuclear protooncogene c-myc began to decrease 30 min after treatment with butyrate and was decreased 4.5-fold 4 h after treatment; however, expression of other immediate-early genes (nup/475 and zif/268) was not significantly affected. Histochemical staining of HT-29 monolayers showed that no cells were positive for alkaline phosphatase protein prior to treatment, and 90% were positive 48 h after treatment. TGF-beta 1 and TGF-beta 2 had no effect on HT-29 cell growth. TGF-beta 1 did not induce alkaline phosphatase mRNA or histochemical positivity. These data indicate that butyrate arrests HT-29 cell growth early in G1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Butyrate rapidly induces growth inhibition and differentiation in HT-29 cells. 837 33

Elevated expression of the c-myc oncogene is a frequent finding in tumors and cell lines derived from carcinomas of the colon and rectum. In a previous study we demonstrated that the differentiation agent sodium butyrate causes a rapid reduction in the expression of c-myc RNA in the rectal carcinoma cell line SW837. This effect was blocked by inhibitors of protein synthesis, suggesting that butyrate causes the induction of an activity that has a negative effect on c-myc expression. In the present work we demonstrate that the rapid decrease in the level of c-myc RNA, upon treatment of SW837 cells with 2 mM butyrate, is followed by a slower decrease in the level of p53 RNA and an increase in the RNA levels for fibronectin and a placental type alkaline phosphatase. Using in vitro elongation of nascent transcripts to measure transcription and actinomycin D chase experiments to measure RNA stability, we show that the reduction in expression of c-myc RNA is due to an increase in the block to transcriptional elongation, rather than a decrease in transcriptional initiation or an increase in degradation of the RNA. We conclude that sodium butyrate induces an activity that increases the transcriptional block in SW837 cells, and that regulation of transcriptional elongation is an important mechanism for regulating c-myc expression in this cell type. A shift in relative usage of the two major promoters in the c-myc gene accompanies the reduction in expression. The potential significance of this finding with respect to transcriptional elongation is discussed. Mutations in the exon 1/intron 1 boundary region of the c-myc gene cause an increase in transcriptional elongation in Burkitt lymphoma. We sequenced this region in a series of cell lines derived from colorectal carcinomas, all of which had an elevated level of c-myc expression, to determine if a similar mutational mechanism is at work in this disease. All of the lines examined had a normal c-myc DNA sequence, suggesting that the deregulation of c-myc expression in colon cancer is not due to a cis mutation in this region.
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PMID:Sodium butyrate causes an increase in the block to transcriptional elongation in the c-myc gene in SW837 rectal carcinoma cells. 837 1

We examined the alterations of proliferative activity and c-myc expression of a colon cancer cell line (Caco-2) during its spontaneous differentiation. Caco-2 cells were cultured in various types of media and the degree of differentiation was monitored in terms of dome formation in cell monolayers and expression of alkaline phosphatase (ALP) activity. In Caco-2 cells cultured with Eagle's minimum essential medium (EMEM) containing 10% fetal calf serum (FCS), dome formation was demonstrated and ALP activity was markedly increased after the cells reached confluence. Five-fold reduction of c-myc mRNA and a marked decrease in S-phase cells were observed in the differentiated cells. These changes were not induced in FCS-free EMEM. The addition of insulin and transferrin to FCS-free EMEM did not induce cell differentiation or reduction of c-myc mRNA expression. When Caco-2 cells were cultured with three different serum-free media, the induction of dome formation and the increase of ALP activity were observed to varying degrees. Expression of c-myc mRNA in the cells cultured with one serum-free medium decreased to a level similar to that in fully differentiated cells cultured with EMEM containing 10% FCS. These results suggest that a spontaneous switch from a proliferative state with high c-myc expression to differentiated phenotype occurs after cells reach confluence and depends on the culture conditions.
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PMID:Changes of proliferative activity and phenotypes in spontaneous differentiation of a colon cancer cell line. 839 33

During a systematic, immunocytochemical screening of 40 human cutaneous melanomas (30 primary and 10 metastatic) for immunophenotype (IP) heterogeneity, we employed a library of 20 well characterized, commercially available mono- and polyclonal antibodies. The use of the sensitive, indirect, four to six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided excellent results. The immunocytochemically most characteristic IP for primary cutaneous melanoma, as detected by us was: HMB45+, S-100+, CEA+, vimentin+, cytokeratin 19+, p53+, Rbgene+, nm23+, HLA-DR+, HL.A-DP+, c-erbB3/HER-3+/-, cytokeratin 10/13+/-, HLA-DQ-, cytokeratin 5/8-, EMA-, c-myc-, and actin-. During melanoma progression, a tendency toward poor differentiation (dedifferentiation) and an increase in c-myc expression have both been observed, the latter downregulating HLA-A,B,C expression and consequently diminishing the possibility of melanoma cell Iysis by powerful CD8+, cytotoxic T lymphocytes (CTL) or other cytotoxic cells which requires HLA class I antigens. The development of the metastatic potential in melanomas caused an increase in CEA expression, eliminated the presence of nm23, and prompted the appearance of actin among the intermediate filaments, composing the cytoskeleton of these malignant tumor cells. The most characteristic IP for MMs, identified by this study was HMB45+, S-100+, CEA+, EMA+, vimentin+, HLA-DR+, HLA-DP+, cytokeratin 19+, actin-, c-erbB3/HER-3+, p53+, cytokeratin 10/13+/-, c-myc+/-, c-erbB2/HER-2+/-, HLA-DQ-, cytokeratin 5/8-, Rb gene-, nm23-. It has been observed that adhesion molecules and integrins play a significant role in the complex process of melanoma metastasis and thus we propose a blocking of these de novo expressed molecules with the appropriate antibodies as a form of immunotherapy of PMs and early stages of MMs.
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PMID:Immunophenotypically varied cell subpopulations in primary and metastatic human melanomas. Monoclonal antibodies for diagnosis, detection of neoplastic progression and receptor directed immunotherapy. 861 65

Cholesteatoma epithelium is characterized by a dysregulation with a hyperproliferative growth and altered differentiation. In a variety of cells c-myc oncogene was found to be highly linked to the control of growth and differentiation. Expression of c-myc was studied in cholesteatoma epithelium using a monoclonal antibody directed against the 67 kDa c-myc protein product and the alkaline phosphatase-antialkaline phosphatase method. For quantitative analysis a computer-linked analyzing system was used. In contrast to normal skin, keratinocytes of basal and suprabasal layers showed nuclear staining in cholesteatoma epithelium. The extent of nuclear staining of epithelial cells in the cholesteatomas studied was significantly increased. Concurrent cytoplasmic staining was observed in both skin and cholesteatoma, but with a stronger reactivity in the latter. These findings suggest participation of the c-myc oncogene in cholesteatoma epithelium.
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PMID:Immunohistochemical demonstration of c-myc oncogene product in middle ear cholesteatoma. 867 57


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