regulation of trib3 mrna and protein in breast cancer监管trib3 mrna和蛋白在乳腺癌.pdfVIP

Regulation of TRIB3 mRNA and Protein in Breast Cancer 1,2 2 3 1 1,2 Marloes Wennemers , Johan Bussink , Twan van den Beucken , Fred C. G. J. Sweep , Paul N. Span * 1 Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 2 Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 3 Department of Radiation Oncology (Maastro Lab), Maastricht University, Maastricht, The Netherlands Abstract Tribbles homolog 3 (TRIB3) is a scaffold protein activated under hypoxic conditions and involved in several cell survival and proliferation pathways. Recently, we reported opposite associations of TRIB3 mRNA and protein with breast cancer prognosis. In this study, we investigated this discrepancy between TRIB3 mRNA and protein in human breast cancer. We provide several lines of evidence demonstrating that TRIB3 is a stabile protein which levels are not controlled by rapid protein breakdown. Interestingly, we were able to show that during anoxia TRIB3 mRNA translation was profoundly inhibited. Hypoxia induced micro RNA 24 was not responsible for the translational repression of TRIB3. Furthermore miRNA- 24 expression levels in breast cancer patient specimens showed no correlation with TRIB3 mRNA or TRIB3 protein levels, or with prognosis. Thus, the expression of miRNA-24 does not explain the difference between mRNA and protein expression of TRIB3 in this cohort of breast cancer patients. In conclusion, TRIB3 protein is a stable protein which levels are predominantly regulated by translational control of TRIB3 mRNA transcript