Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Linoleic and alpha-linolenic acids, obtained from plant material in the diet are the precursors in tissues of two families with opposing effects which are referred to as "essential fatty acids" (EFA): arachidonic acid (AA) and pentaene (eicosapentaenoic acid: EPA) and hexaene (docosahexaenoic acid: DHA) acids. The role of EFA is crucial, without a source of AA or compounds which can be converted into AA, synthesis of prostaglandins (PGs) by a cyclooxygenase (COX) enzyme would be compromised, and this would seriously affect many normal metabolic processes. COX, also known as prostaglandin endoperoxide synthase (Pghs) or as prostaglandin G/H synthase, is a key membrane bound enzyme responsible for the oxidation of AA to PGs. Two COX isoforms have been identified, COX-1 and COX-2 that form PGH2, a common precursor for the biosynthesis of thromboxane A2 (TxA2), prostacyclin (PGI2) and PGs (PGD2, PGE2, PGF2alpha. COX-1 enzyme is expressed constitutively in most cells and tissues. Its expression remains constant under either physiological or pathological conditions controlling synthesis of those PGs primarily involved in the regulation of homeostatic functions. In contrast, COX-2 is an intermediate response gene that encodes a 71-kDa protein. COX-2 is normally absent from most cells but highly inducible in certain cells in response to inflammatory stimuli resulting in enhanced PG release. PGs formed by COX-2 primarily mediate pain and inflammation but have multiple effects that can favour tumorigenesis. They are more abundant in cancers than in normal tissues from which the cancers arise. COX-2 is a participant in the pathway of colon carcinogenesis, especially when mutation of the APC (Adenomatous Polyposis Coli) tumour suppressor gene is the initiating event. In addition, COX-2 up-regulation and elevated PGE2 levels are involved in breast carcinogenesis. It seems that there is a correlation between COX-2 level of expression and the size of the tumours and their propensity to invade underlying tissue. Inhibition by non-steroidal anti-inflammatory drugs (NSAIDs) of COX enzymes which significantly suppress PGE2 levels, reduced breast cancer incidence and protected against colorectal cancer. Therefore it is suggested that consumption of a diet enriched in n-3 PUFA (specifically EPA and DHA) and inhibition of COX-2 by NSAIDs may confer cardioprotective effects and provide a significant mechanism for the prevention and treatment of human cancers.
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PMID:Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. 1219 20

A hallmark of cancer is the paradoxical co-presence, in the same tumour, of local and global DNA hypomethylation together with the regional hypermethylation of certain genes. Due to the oncogenic role of these different DNA methylation alterations, two therapeutic strategies are possible: the use of DNA methylating agents (DMA, such as folate) to inhibit global or local DNA hypomethylation or the use of DNA hypomethylating agents (DHA, such as 5-aza-2-deoxycytidine) to abrogate the accumulation of hypermethylated genes. Here we explored the use of folate to treat gliomas in a mouse model, using tumours induced by either PDGF-B or Ras/Akt overexpression, or by ethylnitrosourea (ENU) treatment. Under all conditions the volume of tumours were significantly less in folate treated mice than in untreated mice. Quantitative methylated DNA immunoprecipitation (qMeDIP) and quantitative methylated specific PCR (qMSP) analysis of methylation status showed that folate treatment, increased the methylation level of DNA repeat elements in tumour and in colorectal tissue and that of MGMT and specific oncogenes (PDGF-B or survivin) in tumours (but not in colorectal tissue), but had no effect on the expression of tumour suppressor genes (p53, PTENorbax) in tumours or in colorectal tissue. This suggests that folate has anti-neoplastic effects in gliomas and that no preneoplastic or neoplastic alterations were observed in unaffected colorectal tissue in response to the potential tumourigenic effects of folate. Collectively, our data support the proposal to include folate as a promising adjuvant in the design of anti-glioma therapeutic protocols in clinical studies.
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PMID:Folate supplementation limits the tumourigenesis in rodent models of gliomagenesis. 2232 70