FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1975682279> ?p ?o ?g. }

• W1975682279 abstract "Background: Agents that introduce genotoxic stresses in mammalian cells, such as paclitaxel (Taxol) or ionizing radiation activate a complex array of cellular responses, including p53 activation. As a component of the response to acute stress, p53 has a well-established role in protecting against cancer development. It is not surprising that half of all human tumors have mutated p53. We asked how then tumors are initiated in the cells that carry wild-type p53 allele?Material and Methods: Here we report the identification of a potential novel mechanism that induces tumor formation in p53 wild-type cells. Overexpression of the proto-oncogene, BRCA1-IRIS in human mammary epithelial (HME) cells not only upregulates the expression of the serine/threonine phosphatase; Wild-type p53-Induced Phosphatase (WIP1) through induction of p53 expression but also increases the WIP1 gene copy number in these cells. WIP1 is a negative regulator of p53 as well as p38MAPK. Both proteins are involved in arresting and/or killing cells with extensive genotoxic stresses. Failure to arrest or die in response to massive genotoxic stress leads to the propagation of damaged cells and the development of cancer. BRCA1-IRIS overexpressing cells failed to arrest or die when exposed to UV radiation or Taxol. In fact, treatment of normal HME cells with UV or Taxol upregulated the expression of BRCA1-IRIS and thus WIP-1, prevented p53 and p38MAPK activation and their death.Results: This data suggest that BRCA1-IRIS is perhaps involved in the acquisition of cellular resistance to these agents upon prolonged exposure. On the other hand, depletion of BRCA1-IRIS from tumor cell lines induced apoptosis even in cells with functional p53 and p38MAPK.Discussion: We propose that in p53 wild type cells, whether endogenous or UV- or chemotherapy-induced BRCA1-IRIS overexpression leads to the survival and proliferation of what most likely are severely damaged cells, leading to the transformation of mammary cells in vitro and the induction of breast tumors in vivo. We also propose that BRCA1-IRIS and WIP1 overexpression abrogates the homeostatic balance maintained by p38-p53-WIP1 pathway. Together with the ability of BRCA1-IRIS to upregulate Cyclin D1 expression increases the likelihood that BRCA1-IRIS is an oncogene that induces breast cancer progression when overexpressed, hence making it an attractive target for novel breast cancer therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3154." @default.
• W1975682279 created "2016-06-24" @default.
• W1975682279 creator A5082883577 @default.
• W1975682279 date "2009-12-15" @default.
• W1975682279 modified "2023-09-30" @default.
• W1975682279 title "Induction of Aggressive Breast Cancer in p53 Wild Type Cells by BRCA1-IRIS Overexpression." @default.
• W1975682279 doi "https://doi.org/10.1158/0008-5472.sabcs-09-3154" @default.
• W1975682279 hasPublicationYear "2009" @default.
• W1975682279 type Work @default.
• W1975682279 sameAs 1975682279 @default.
• W1975682279 citedByCount "0" @default.
• W1975682279 crossrefType "proceedings-article" @default.
• W1975682279 hasAuthorship W1975682279A5082883577 @default.
• W1975682279 hasConcept C104317684 @default.
• W1975682279 hasConcept C121608353 @default.
• W1975682279 hasConcept C127561419 @default.
• W1975682279 hasConcept C134935766 @default.
• W1975682279 hasConcept C143425029 @default.
• W1975682279 hasConcept C502942594 @default.
• W1975682279 hasConcept C54355233 @default.
• W1975682279 hasConcept C552990157 @default.
• W1975682279 hasConcept C86803240 @default.
• W1975682279 hasConcept C96232424 @default.
• W1975682279 hasConceptScore W1975682279C104317684 @default.
• W1975682279 hasConceptScore W1975682279C121608353 @default.
• W1975682279 hasConceptScore W1975682279C127561419 @default.
• W1975682279 hasConceptScore W1975682279C134935766 @default.
• W1975682279 hasConceptScore W1975682279C143425029 @default.
• W1975682279 hasConceptScore W1975682279C502942594 @default.
• W1975682279 hasConceptScore W1975682279C54355233 @default.
• W1975682279 hasConceptScore W1975682279C552990157 @default.
• W1975682279 hasConceptScore W1975682279C86803240 @default.
• W1975682279 hasConceptScore W1975682279C96232424 @default.
• W1975682279 hasLocation W19756822791 @default.
• W1975682279 hasOpenAccess W1975682279 @default.
• W1975682279 hasPrimaryLocation W19756822791 @default.
• W1975682279 hasRelatedWork W1805188088 @default.
• W1975682279 hasRelatedWork W1966147273 @default.
• W1975682279 hasRelatedWork W1993446755 @default.
• W1975682279 hasRelatedWork W2004083214 @default.
• W1975682279 hasRelatedWork W2057961158 @default.
• W1975682279 hasRelatedWork W2063208692 @default.
• W1975682279 hasRelatedWork W2099186537 @default.
• W1975682279 hasRelatedWork W2125236946 @default.
• W1975682279 hasRelatedWork W2224899546 @default.
• W1975682279 hasRelatedWork W2325875125 @default.
• W1975682279 hasRelatedWork W2402334134 @default.
• W1975682279 hasRelatedWork W2414107358 @default.
• W1975682279 hasRelatedWork W2503230196 @default.
• W1975682279 hasRelatedWork W2739605790 @default.
• W1975682279 hasRelatedWork W2762521153 @default.
• W1975682279 hasRelatedWork W2905588185 @default.
• W1975682279 hasRelatedWork W2988051531 @default.
• W1975682279 hasRelatedWork W3109063469 @default.
• W1975682279 hasRelatedWork W3147530535 @default.
• W1975682279 hasRelatedWork W3212690720 @default.
• W1975682279 isParatext "false" @default.
• W1975682279 isRetracted "false" @default.
• W1975682279 magId "1975682279" @default.
• W1975682279 workType "article" @default.