BCL2 antagonist of cell death kinases, phosphatases, and ovarian cancer sensitivity to cisplatin.

Journal of Gynecologic Oncology
Nisha BansalJohnathan M Lancaster

Abstract

The BCL2 family proteins are critical mediators of cellular apoptosis and, as such, have been implicated as determinants of cancer cell chemo-sensitivity. Recently, it has been demonstrated that the phosphorylation status of the BCL2 antagonist of cell death (BAD) protein may influence ovarian cancer (OVCA) cell sensitivity to cisplatin. Here, we sought to evaluate how kinase and phosphatase components of the BAD apoptosis pathway influence OVCA chemo-sensitivity. Protein levels of cyclin-dependent kinase 1 (CDK1) and protein phosphatase 2C (PP2C) were measured by immunofluorescence in a series of 64 primary advanced-stage serous OVCA patient samples. In parallel, levels of cAMP-dependent protein kinase (PKA), AKT, and PP2C were quantified by Western blot analysis in paired mother/daughter platinum-sensitive/resistant OVCA cell lines (A2008/C13, A2780S/A2780CP, Chi/ChiR). BAD pathway kinase CDK1 was depleted using siRNA transfection, and the influence on BAD phosphorylation and cisplatin-induced apoptosis was evaluated. OVCA patient samples that demonstrated complete responses to primary platinum-based therapy demonstrated 4-fold higher CDK1 (p<0.0001) and 2-fold lower PP2C (p=0.14) protein levels than samples that demonstrated...Continue Reading

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Citations

May 23, 2012·Journal of Translational Medicine·Jiri SanaOndrej Slaby
Mar 19, 2013·Oncogene·J StebbingG Giamas
Feb 6, 2015·International Journal of Molecular Medicine·Xiaomang B SticklesJohnathan M Lancaster
Mar 8, 2018·Journal of Experimental & Clinical Cancer Research : CR·Dong-Dong ChengQing-Cheng Yang
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Nov 27, 2019·Scientific Reports·Bernadette M BoacDouglas C Marchion
Jan 21, 2017·Experimental and Therapeutic Medicine·Xing-Hua WangYan-Ping Ni
Aug 13, 2017·The Biochemical Journal·Matthias DedobbeleerBernard Rogister

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Methods Mentioned

BETA
transfection
fluorescence microscopy

Software Mentioned

Image Pro Plus

Related Concepts

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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