Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GIPC1/GIPC/RGS19IP1, GIPC2, and GIPC3 genes constitute the human GIPC gene family. GIPC1 and GIPC2 show 62.0% total-amino-acid identity. GIPC1 and GIPC3 show 59.9% total-amino-acid identity. GIPC2 and GIPC3 show 55.3% total-amino-acid identity. GIPCs are proteins with central PDZ domain and GIPC homology (GH1 and GH2) domains. PDZ, GH1, and GH2 domains are conserved among human GIPCs, Xenopus GIPC/Kermit, and Drosophila GIPC/ LP09416. Bioinformatics revealed that GIPC genes are linked to prostanoid receptor genes and DNAJB genes in the human genome as follows: GIPC1 gene is linked to prostaglandin E receptor 1 (PTGER1) gene and DNAJB1 gene in human chromosome 19p13.2-p13.1 region; GIPC2 gene to prostaglandin F receptor (PTGFR) gene and DNAJB4 gene in human chromosome 1p31.1-p22.3 region; GIPC3 gene to thromboxane A2 receptor (TBXA2R) gene in human chromosome 19p13.3 region. GIPC1 and GIPC2 mRNAs are expressed together in OKAJIMA, TMK1, MKN45 and KATO-III cells derived from diffuse-type of gastric cancer, and are up-regulated in several cases of primary gastric cancer. PDZ domain of GIPC family proteins interact with Frizzled-3 (FZD3) class of WNT receptor, insulin-like growth factor-I (IGF1) receptor, receptor tyrosine kinase TrkA, TGF-beta type III receptor (TGF-beta RIII), integrin alpha6A subunit, transmembrane glycoprotein 5T4, and RGS19/RGS-GAIP. Because RGS19 is a member of the RGS family that regulate heterotrimeric G-protein signaling, GIPCs might be scaffold proteins linking heterotrimeric G-proteins to seven-transmembrane-type WNT receptor or to receptor tyrosine kinases. Therefore, GIPC1, GIPC2 and GIPC3 might play key roles in carcinogenesis and embryogenesis through modulation of growth factor signaling and cell adhesion.
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PMID:GIPC gene family (Review). 1201 74

The biological functions of some orthologs within the human genome and model-animal genomes are evolutionarily conserved, but those of others are divergent due to protein evolution and promoter evolution. Because WNT signaling molecules play key roles during embryogenesis, tissue regeneration and carcinogenesis, the author's group has carried out a human WNT-ome project for the comprehensive characterization of human genes encoding WNT signaling molecules. From 1996 to 2002, we cloned and characterized WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT9A/WNT14, WNT9B/WNT14B, WNT10A, WNT10B, WNT11, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD10, FRAT1, FRAT2, NKD1, NKD2, VANGL1, RHOU/ARHU, RHOV/ARHV, GIPC2, GIPC3, FBXW11/betaTRCP2, SOX17, TCF7L1/TCF3, and established a cDNA-PCR system for snap-shot and dynamic analyses on the WNT-transcriptome. In 2003, we identified and characterized PRICKLE1, PRICKLE2, DACT1/DAPPER1, DACT2/DAPPER2, DAAM2, and BCL9L. After completion of the human WNT-ome project, we have been working on the stem cell signaling network. WNT signals are transduced to beta-catenin, NLK, NFAT, PKC, JNK and RhoA signaling cascades. FGF20, JAG1 and DKK1 are target genes of the WNT-beta-catenin signaling cascade. Cross-talk of WNT and FGF signaling pathways potentiates beta-catenin and NFAT signaling cascades. BMP signals induce IHH upregulation in co-operation with RUNX. Hedgehog signals induce upregulation of SFRP1, JAG2 and FOXL1, and then FOXL1 induces BMP4 upregulation. The balance between WNT-FGF-Notch and BMP-Hedgehog signaling networks is important for the maintenance of homoestasis among stem and progenitor cells. Disruption of the stem cell signaling network results in pathological conditions, such as congenital diseases and cancer.
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PMID:Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. 1787 79

Nickel(II), capable of transforming cells and causing tumors in humans and animals, has been previously shown by us to mediate hydrolytic truncation of histone H2A's C-terminal tail by 8 amino acids in both cell-free and cell culture systems. Since H2A's C-tail is involved in maintaining chromatin structure, such truncation might alter this structure and affect gene expression. To test the latter possibility, we transfected cultured T-REx 293 human embryonic kidney cells with plasmids expressing either wild type (wt) or truncated (q) histone H2A proteins, which were either untagged or N-terminally tagged with fluorescent proteins. Each histone variant was found to be incorporated into chromatin at 24 and 48 hr post-transfection. Cells transfected with the untagged plasmids were tested for gene expression by microarray and real-time PCR. Evaluation of the results for over 21,000 genes using the multidimensional scaling and hierarchical clustering methods revealed significant differences in expression of numerous genes between the q-H2A and wt-H2A transfectants. Many of the differentially expressed genes, including BAZ2A, CLDN18, CYP51A1, GFR, GIPC2, HMGB1, IRF7, JAK3, PSIP1, and VEGF, are cancer-related genes. The results thus demonstrate the potential of q-H2A to contribute to the process of carcinogenesis through epigenetic mechanisms.
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PMID:Truncation of histone H2A's C-terminal tail, as is typical for Ni(II)-assisted specific peptide bond hydrolysis, has gene expression altering effects. 1966 9

The intriguing molecular pathways involved in oral carcinogenesis are still ambiguous. The oral squamous cell carcinoma (OSCC) ranks as the most common type constituting more than 90% of the globally diagnosed oral cancers cases. The elevation in the OSCC incidence rate during past 10 years has an alarming impression on human healthcare. The major challenges associated with OSCC include delayed diagnosis, high metastatic rates, and low 5-year survival rates. The present work foundations on reverse genetic strategy and involves the identification of genes showing expressional variability in an OSCC case lacking addictive proclivities for tobacco, betel nut, and/or alcohol, major etiologies. The expression modulations in the identified genes were analyzed in 16 patients comprising oral pre-cancer and cancer histo-pathologies. The genes SCCA1 and KRT1 were found to down regulate while DNAJC13, GIPC2, MRPL17, IG-Vreg, SSFA2, and UPF0415 upregulated in the oral pre-cancer and cancer pathologies, implicating the genes as crucial players in oral carcinogenesis.
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PMID:Assessment of cellular and serum proteome from tongue squamous cell carcinoma patient lacking addictive proclivities for tobacco, betel nut, and alcohol: Case study. 2923 89