Stat3 upregulates MEK5 expression in human breast cancer cells

Oncogene
Hui SongJiayuh Lin

Abstract

The constitutive activation of signal transducer and activator of transcription 3 (Stat3) is frequently detected in breast cancer cell lines but not in normal breast epithelial cells. Stat3 has been classified as an oncogene, because constitutively active Stat3 can mediate oncogenic transformation in cultured cells and tumor formation in nude mice. Since Stat3 appears to play an important role in breast cancer, it is of interest to investigate Stat3-regulated genes and elucidate Stat3-mediated oncogenesis. In this study, we investigated the Stat3-regulated genes in human breast epithelial cells. Upon overexpression of Stat3-C, a constitutively active Stat3 form, in nonmalignant telomerase immortalized breast (TERT) cells, the total mRNA was extracted and subjected to Affymetrix microarray analysis. Our results showed that mitogen-activated protein kinase kinase 5 (MEK5) was markedly induced (more than 22-fold increase, P<0.001) by Stat3-C expression. RT-PCR result also demonstrated that MEK5 mRNA was significantly induced by Stat3-C in TERT cells. The upregulation of MEK5 by Stat3-C was further confirmed by Western blot in MCF10A breast epithelial cells. Furthermore, in MDA-MB-435s breast carcinoma cells, which express high lev...Continue Reading

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