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Suppressor Pathway (suppressor + pathway)

Distribution by Scientific Domains
Medical Sciences66%
Life Sciences22%

Kinds of Suppressor Pathway

  • tumor suppressor pathway
    		•

    Selected Abstracts

    Creation of psoriatic plaques: the ultimate tumor suppressor pathway.

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2001
    A new model for an ancient T-cell-mediated skin disease.
    From an oncological and immunological perspective, the T-cell-mediated induction of psoriatic plaques should be prone to malignant transformation as the phenotype of psoriatic plaques includes: chronic inflammation, epidermal hyperplasia, prolonged survival and elevated telomerase levels in lesional keratinocytes, as well as angiogenesis, exposure to carcinogens and immunosuppressants. However, conversion of a psoriatic plaque to squamous cell carcinoma is exceedingly rare. This paper explores the possible molecular mechanism for the tumor suppressor pathway in psoriatic lesions, with an emphasis on a putative senescence-switch involving p16. [source]

    Microsatellite instability in esophageal squamous cell carcinoma is not associated with hMLH1 promoter hypermethylation

    PATHOLOGY INTERNATIONAL, Issue 5 2003
    Masahiro Hayashi
    To test whether a subset of esophageal squamous cell carcinomas (SCC) develop through a deficiency in DNA mismatch repair, we examined microsatellite instability (MSI) using 11 microsatellite markers including BAT-26, hMLH1 protein expression by immunohistochemistry, and methylation status of the hMLH1 promoter by methylation-specific polymerase chain reaction (MSP). p53 mutations were also investigated. Microsatellite instability at one or more loci was observed in 40% (12/30) of esophageal SCC tumor samples, although only one of these tumors was categorized as high-frequency MSI (MSI-H) and none showed BAT-26 instability. While immunohistochemistry revealed decreased hMLH1 protein expression in 27% (8/30) of the tumors, hMLH1 promoter hypermethylation was not observed. Absence of hMLH1 protein expression was relatively common in well-differentiated (keratinizing-type) esophageal SCC, but was not associated with hMLH1 promoter hypermethylation. p53 mutation was detected in 37% (11/30) and loss of heterozygosity (LOH) in 90% (27/30) of esophageal SCC samples. Our results suggested that most esophageal SCC develop through defects in tumor suppressor genes (i.e. the suppressor pathway), and that MSI in esophageal SCC probably represent random replication errors rather than being associated with DNA mismatch repair deficiency. [source]

    MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: A report from the Children's Oncology Group,

    PEDIATRIC BLOOD & CANCER, Issue 2 2010
    Christine L. Phillips MD
    Abstract Background The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li,Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have 10-fold increase resistance to topoisomerase II inhibitors in vitro. Procedure We genotyped children (n,=,575) with de novo acute myeloid leukemia (AML) treated on three Children's Oncology Group protocols (CCG 2941/2961/AAML 03P1) for the presence of SNP309. Healthy blood donors were genotyped as control population. Results The variant G/G genotype was associated with an increased susceptibility to AML (OR 1.5; P,=,0.049). However, the presence of the variant allele at SNP309 did not modify disease response or toxicity in children treated on CCG protocols 2941/2961. Conclusions The variant SNP 309 influences susceptibility to pediatric AML, but does not impact overall response to therapy. Pediatr Blood Cancer. 2010;55:248,253. © 2010 Wiley,Liss, Inc. [source]

    ID2-VEGF-related Pathways in the Pathogenesis of Kaposi's Sarcoma: A Link Disrupted by Rapamycin

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009
    G. Stallone
    The Id-proteins are a family of four related proteins implicated in the control of differentiation and cell-cycle progression. Down-regulation of Id-gene expression is essential for the differentiation of several cell types. In addition, deregulated Id2 activity inhibits the Rb tumor suppressor pathway and promotes the expression of vascular endothelial growth factor (VEGF). Several members of VEGF family could be involved in Kaposi's sarcoma (KS) development and progression. Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is the first marker of lymphatic endothelial competence during development in the mature vasculature, and is also expressed on KS spindle cells. Rapamycin (RAPA), an immunosuppressive drug, has been shown to reverse KS growth and to reduce tumor angiogenesis. We evaluate, in transplantation-associated KS and in cultured KS-cells the RAPA effect on Id2 and on de novo lymphangiogenesis. Markers of lymphatic-endothelial-cells (VEGFR-3, LYVE-1) and Id2, expressed at low levels within the normal skin, were up-regulated in KS and returned to normal levels after RAPA introduction. The association between Id2 and lymphangiogenesis is suggested by co-localization of Id2, VEGFR-3 and LYVE-1. RAPA inhibition on Id2 expression was confirmed in vitro in KS-cells, both in basal conditions and upon stimulation with VEGF. In conclusion, our data would suggest a novel molecular mechanism for the antineoplastic effects of RAPA in posttransplant KS. [source]

    The E8 repression domain can replace the E2 transactivation domain for growth inhibition of HeLa cells by papillomavirus E2 proteins

    INTERNATIONAL JOURNAL OF CANCER, Issue 10 2007
    Frank Stubenrauch
    Abstract Continuous expression of the human papillomavirus (HPV) oncoproteins E6 and E7 is required for the growth of cervical cancer cell lines. So far, only the overexpression of the wild type papillomavirus E2 protein has been shown to induce growth arrest in HPV18-positive HeLa cells by repressing E6/E7 transcription. Growth arrest by E2 requires the aminoterminal transcription activation domain in addition to the carboxyterminal DNA-binding domain. Several papillomaviruses such as the carcinogenic HPV31 express in addition to E2 an E8,E2C fusion protein in which the E8 domain, which is required for repression of replication and transcription, replaces the E2 activation domain. In this report, we demonstrate that the HPV31 E8,E2C protein is able to inhibit the growth of HeLa cells but not of HPV-negative C33A cervical cancer cells. Growth repression by E8,E2C correlates with repression of the endogenous HPV18 E6/E7 promoter and the reappearance of E6- and E7-regulated p53, pRb and p21 proteins, suggesting that E8,E2C inhibits growth by reactivating dormant tumor suppressor pathways. Growth inhibition requires an intact E8 repression domain in addition to the carboxyterminal E2C DNA binding domain. Chromatin immunoprecipitation experiments suggest that the E8 repression domain enhances binding to the HPV18 promoter sequence in vivo. In summary, our results demonstrate that the small E8 repression domain can functionally replace the large E2 transactivation domain for growth inhibition of HeLa cervical cancer cells. © 2007 Wiley-Liss, Inc. [source]

    Involvement of the INK4a/Arf gene locus in senescence

    AGING CELL, Issue 3 2003
    Carol J. Collins
    Summary The INK4a/ARF locus encodes two proteins whose expression limits cellular proliferation. Whilst the biochemical activities of the two proteins appear very different, they both converge on regulating the retinoblastoma and p53 tumour suppressor pathways. Neither protein is required for normal development, but lack of either predisposes to the development of malignancy. Both proteins have also been implicated in the establishment of senescence states in response to a variety of stresses, signalling imbalances and telomere shortening. The INK4a/Arf regulatory circuits appear to be partially redundant and show evidence of rapid evolution. Especially intriguing are the large number of biological differences documented between mice and man. We review here the brief history of INK4a/Arf and explore possible links with organismal aging and the evolution of longevity. [source]

    Proteomic and SAGE profiling of murine melanoma progression indicates the reduction of proteins responsible for ROS degradation

    PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2006
    Gustavo A. de Souza
    Abstract Using 2-DE of total cell protein extracts, we compared soluble proteins from murine melanoma lines Tm1 and Tm5 with proteins from the nontumoral cell melan-a from which they were derived. Seventy-one of the 452 spots (average) detected with CBB were differentially accumulated, i.e., increased or decreased twofold. Forty-four spots were identified by PMF/MALDI-TOF, 15 with increased and 29 with decreased protein levels. SAGE showed that 17/34 (50%) of the differentially accumulated proteins, pI range 4,7, presented similar differences at the mRNA level. Major reductions in protein were observed in tumor cells of proteins that degrade reactive oxygen species (ROS). Decreases of , twofold in GST, superoxide dismutase, aldehyde dehydrogenase, thioredoxin, peroxiredoxin 2, and peroxiredoxin 6 protein were observed. SAGE indicated the reduction of other proteins involved in ROS degradation. As expected, the accumulation of exogenous peroxides was significantly higher in the tumor cells while the levels of glutathionylation were two times lower in the tumor cells compared to melan-a. The differential accumulation of proteins involved in oncogene/tumor suppressor pathways was observed. Melanoma cells can favor survival pathways activated by ROS by inhibiting p53 pathways and activation of Ras and c-myc pathways. [source]

    Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling

    BIOFACTORS, Issue 4 2009
    Alexander Hergovich
    Abstract The NDR/LATS family of kinases is a subgroup of the AGC group of protein kinases and is conserved from lower eukaryotes to humans. Like other AGC kinases, NDR/LATS kinases require phosphorylation of conserved Ser/Thr residues for activation. On the one hand, binding of the coactivator MOB to NDR/LATS allows autophosphorylation. On the other hand, MST kinases directly phosphorylate NDR/LATS kinases. In addition to our understanding of the molecular activation mechanisms, recent studies have shown that LATS kinases play a central role in Hippo/SWH (Salvador/Warts/Hippo) tumor suppressor pathways, which coordinate cell proliferation and apoptosis by regulating proto-oncogenes, such as YAP and TAZ. In this review, we summarize current knowledge of Merlin/MST/SAV/MOB/LATS/NDR/YAP/TAZ networks (also termed mammalian Hippo signaling) and their roles in mammalian cellular transformation. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source]