BACKGROUND: Tribbles homolog 3 (TRIB3) is a pseudokinase involved in the regulation of several signaling pathways involved in cell survival and/or cell stress. Here, we determined the correlation between breast cancer prognosis and TRIB3 protein levels and established the role of TRIB3 in cell survival after hypoxia and/or radiotherapy. MATERIAL AND METHODS: TRIB3 mRNA and protein were quantified in a new independent breast cancer patient cohort using QPCR and a new specific avian antibody against TRIB3. In addition, we used siRNA-mediated knockdown of TRIB3 in a colony-forming assay after hypoxia and radiotherapy. RESULTS: TRIB3 mRNA and protein levels did not correlate in breast cancer cell lines or human breast cancer material. We validated our earlier finding that high TRIB3 mRNA denotes a poor prognosis, but found that high TRIB3 protein levels were associated with a good prognosis in breast cancer patients. We also show that knockdown of TRIB3 resulted in an increased survival under hypoxic conditions. CONCLUSION: Whereas mRNA levels of TRIB3 are related with a poor prognosis, TRIB3 protein is associated with a good prognosis in human breast cancer patients, possibly due to the fact that TRIB3 is involved in hypoxia tolerance. Copyright Â
BACKGROUND:Tribbles homolog 3 (TRIB3) is a pseudokinase involved in the regulation of several signaling pathways involved in cell survival and/or cell stress. Here, we determined the correlation between breast cancer prognosis and TRIB3 protein levels and established the role of TRIB3 in cell survival after hypoxia and/or radiotherapy. MATERIAL AND METHODS:TRIB3 mRNA and protein were quantified in a new independent breast cancerpatient cohort using QPCR and a new specific avian antibody against TRIB3. In addition, we used siRNA-mediated knockdown of TRIB3 in a colony-forming assay after hypoxia and radiotherapy. RESULTS:TRIB3 mRNA and protein levels did not correlate in breast cancer cell lines or humanbreast cancer material. We validated our earlier finding that high TRIB3 mRNA denotes a poor prognosis, but found that high TRIB3 protein levels were associated with a good prognosis in breast cancerpatients. We also show that knockdown of TRIB3 resulted in an increased survival under hypoxic conditions. CONCLUSION: Whereas mRNA levels of TRIB3 are related with a poor prognosis, TRIB3 protein is associated with a good prognosis in humanbreast cancerpatients, possibly due to the fact that TRIB3 is involved in hypoxia tolerance. Copyright Â
Authors: Julia Izrailit; Hal K Berman; Alessandro Datti; Jeffrey L Wrana; Michael Reedijk Journal: Proc Natl Acad Sci U S A Date: 2013-01-14 Impact factor: 11.205
Authors: M Salazar; M Lorente; E García-Taboada; E Pérez Gómez; D Dávila; P Zúñiga-García; J María Flores; A Rodríguez; Z Hegedus; D Mosén-Ansorena; A M Aransay; S Hernández-Tiedra; I López-Valero; M Quintanilla; C Sánchez; J L Iovanna; N Dusetti; M Guzmán; S E Francis; A Carracedo; E Kiss-Toth; G Velasco Journal: Cell Death Differ Date: 2014-08-29 Impact factor: 15.828
Authors: Sylvie M Noordermeer; Marloes Wennemers; Saskia M Bergevoet; Adrian van der Heijden; Evelyn Tönnissen; Fred C G J Sweep; Joop H Jansen; Paul N Span; Bert A van der Reijden Journal: Breast Cancer Res Treat Date: 2012-06-16 Impact factor: 4.872