Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion to fibronectin through the alpha5beta1 integrin enables endothelial cells to proliferate in response to growth factors, whereas adhesion to laminin through alpha2beta1 results in growth arrest under the same conditions. On laminin, endothelial cells fail to translate Cyclin D1 mRNA and activate CDK4 and CDK6. Activated Rac, but not MEK1, PI-3K, or Akt, rescues biosynthesis of cyclin D1 and progression through the G(1) phase. Conversely, dominant negative Rac prevents these events on fibronectin. Mitogens promote activation of Rac on fibronectin but not laminin. This process is mediated by SOS and PI-3K and requires coordinate upstream signals through Shc and FAK. These results indicate that Rac is a crucial mediator of the integrin-specific control of cell cycle in endothelial cells.
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PMID:Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle. 1151 65

1-SO-adenine DNA adducts, DNA single-strand breaks (SBs), chromosomal aberrations (CAs), mutant frequency (MF) at the HPRT gene, and immune parameters (hematological and of humoral immunity) were studied in styrene-exposed human subjects and controls. Results were correlated with genetic polymorphisms in DNA repair genes (XPD, exon 23, XPG, exon 15, XPC, exon 15, XRCC1, exon 10, XRCC3, exon 7) and cell cycle gene cyclin D1. Results for biomarkers of genotoxicity after stratification for the different DNA repair genetic polymorphisms showed that the polymorphism in exon 23 of the XPD gene modulates levels of chromosomal and DNA damage, HPRT MF, and moderately affects DNA adduct levels. The highest levels of biomarkers were associated with the wild-type homozygous AA genotype. The exposed individuals with the wild-type GG genotype for XRCC1 gene exhibited the lowest CA frequencies, compared to those with an A allele (P < 0.05). Cyclin D1 polymorphism seems to modulate the number of leukocytes and lymphocytes in the analyzed subjects. The number of eosinophiles was positively associated with XPD variant C allele and negatively with XRCC1 variant A allele (P < 0.05) and XPC variant C allele (P < 0.05). Immunoglobulin IgA was positively associated with an XRCC3 variant T allele (P < 0.01) and negatively with XPC variant C allele (P < 0.05). Both C3- and C4-complement components were lower in individuals with XRCC3 CT (P < 0.05) and TT genotypes (P < 0.01). Adhesion molecules sL-selectin and sICAM-1 were associated with XPC genotype (P < 0.05). Individual susceptibility may be reflected in genotoxic and immunotoxic responses to environmental and occupational exposures to xenobiotics.
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PMID:DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity. 1599 42

Pentoxifylline (PTX) is a methylxanthine derivative currently being used in the treatment of peripheral vascular diseases. Recently, we had evaluated its action in human MDA-MB-231 breast cancer cells. PTX exhibited anti-metastatic activity by affecting key processes such as proliferation, adhesion, migration, invasion and apoptosis. In light of the preliminary findings, the present work accounts for the possible mechanistic insights of the pathways affected by PTX. Aberrant Focal Adhesion Kinase (FAK) signaling forms a key determinant in breast cancer and in view of this fact we had investigated downstream processes regulated by FAK. PTX at sub-toxic doses lowers the level of activated FAK, Extracellular Regulated Kinase or Mitogen Activated Protein Kinase (ERK/MAPK), Protein Kinase B (PKB/Akt) affecting cellular proliferation and survival. It blocks G1/S phase of cell cycle by inhibiting the expression of Cyclin D1/Cdk6. Further, it modulates the activities of RhoGTPases and alters actin organization resulting in decreased motility. PTX also delays tumor growth and inhibited blood vessel formation in vivo. In purview of these findings, PTX surely qualifies as a suitable prospect in the intervention of breast cancer.
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PMID:Curbing the focal adhesion kinase and its associated signaling events by pentoxifylline in MDA-MB-231 human breast cancer cells. 2387 75