The Involvement of S6 Kinase-2 in Breast Cancer




Basu, Alakananda
Joshi, Rohan


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Purpose: Breast cancer is the second leading cause of cancer death in women. Triple negative breast cancer is characterized by the lack of estrogen receptor, progesterone receptor, and HER2/neu and hence poses a problem for targeted therapy. Thus there is an urgent need to identify a suitable molecular target. The 40S ribosomal protein S6 kinase (S6K) acts downstream of mTOR, which plays important roles in cell proliferation, protein translation, and cell survival and is a potential target for cancer therapy. S6K exists as two homologues, S6K-1 and S6K-2, but little is known about the function of S6K-2. Although Akt is believed to act upstream of mTOR, persistent inhibition of S6K-1 can activate Akt via a negative feedback loop. In the present study, we have examined the effects of S6K-2 on Bcl-2. Bcl-2 is in the Bcl-2 family of proteins and is an anti-apoptotic protein. Methods: The breast cancer cell lines ZR-75 and MCF-7 were used. These cells were transfected using siRNAs which were either control non-targeting or target-specific. The extent of gene knockdown was determined by Western blot analysis. The proteins from the cell extract were visualized using SDS-PAGE gel electrophoresis and enhanced chemiluminescence. Yo-Pro staining was used to visualize apoptotic cells. Results: It was noted that S6K-2 knockdown lead to a decrease in Bcl-2, this occurred concurrently with an increase in cell death. Silencing of S6K-2 caused a decrease in Bcl-2 via Akt. Conclusion: Targeting S6K-2 may be an effective therapeutic strategy to treat breast cancer.