Figure 7

Stat3 pathway contributes to Jab1 transcriptional activation and increased protein levels. (a) Increased expression of Stat3 in the normal mammary epithelial MCF-10A cells increased Jab1 RNA levels as detected by RTPCR, quantification of Jab1 RNA levels is shown in the bottom panel. (b) Ectopic expression of Flag-Stat3 (0, 1, 2, and 3 μg) in normal mammary epithelial cells (MCF-10A and MCF-10F) resulted in increased Jab1 protein levels. (c) Treatment with the cytokine IL-6 increased Jab1 mRNA levels - seen by RT-PCR - in both normal MCF-10A and breast cancer T47D cells that were blocked by the Stat3 inhibitor Stattic. (d) Treatment with IL-6 increased Jab1 protein levels following activation of Stat3 (P-Stat3 Y705) that was inhibited by the addition of Stattic. (e) Schematic representation of the major molecular mechanism of Stat3-induced transcriptional activation of Jab1 through two signaling axes - Src/Stat3 and IL-6/Stat3. Jab1, c-Jun activation domain-binding protein-1; RT-PCR, reverse transcription polymerase chain reaction; STAT, signal transducer and activator of transcription.