Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands.
Radiother Oncol. 2011 Oct;101(1):198-202. doi: 10.1016/j.radonc.2011.05.057. Epub 2011 Jun 23.
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.
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.
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.
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.
Tribbles 同源物 3（TRIB3）是一种参与调节细胞存活和/或细胞应激的几种信号通路的拟激酶。在这里，我们确定了 TRIB3 蛋白水平与乳腺癌预后之间的相关性，并确定了 TRIB3 在缺氧和/或放射治疗后细胞存活中的作用。
使用 QPCR 和针对 TRIB3 的新型特异性禽抗体在新的独立乳腺癌患者队列中定量测定 TRIB3 mRNA 和蛋白。此外，我们还在缺氧和放射治疗后的集落形成试验中使用 siRNA 介导的 TRIB3 敲低。
TRIB3 mRNA 和蛋白水平在乳腺癌细胞系或人乳腺癌材料中没有相关性。我们验证了我们之前的发现，即高 TRIB3 mRNA 表示预后不良，但发现高 TRIB3 蛋白水平与乳腺癌患者的良好预后相关。我们还表明，TRIB3 的敲低导致在缺氧条件下存活能力增加。
虽然 TRIB3 的 mRNA 水平与预后不良有关，但 TRIB3 蛋白与人类乳腺癌患者的良好预后相关，这可能是因为 TRIB3 参与了缺氧耐受。
