BACKGROUND: Caner-initiating cells (CICs or cancer stem cells) have been shown both experimentally and clinically to be resistant to radiation. The mechanism underlying radioresistance remains unclear. METHODS: In the present study, we screened 51 genes which are potentially important in mediating radioresistance of breast CICs. RESULTS: The expression of AKT1 and AKT2 at protein and mRNA levels was dramatically increased among the screened genes by 8 Gy radiation treatment in MCF-7 mammosphere cells (predominantly CD24(-/low)/CD44(+) CICs), but not in the bulk population of MCF-7 cells (predominantly CD24(+)/CD44(+)). Using apoptosis and clonogenic survival assays, we found pharmacological inhibition of AKT with selective inhibitors of AKT sensitized MCF-7 mammosphere cells, but not MCF-7 monolayer cells to radiation. CONCLUSION: The present findings suggest that treatment with AKT inhibitors prior to ionizing radiation treatment may be a potential benefit to patients with breast cancer, in particular to eradiate breast CICs.
BACKGROUND: Caner-initiating cells (CICs or cancer stem cells) have been shown both experimentally and clinically to be resistant to radiation. The mechanism underlying radioresistance remains unclear. METHODS: In the present study, we screened 51 genes which are potentially important in mediating radioresistance of breast CICs. RESULTS: The expression of AKT1 and AKT2 at protein and mRNA levels was dramatically increased among the screened genes by 8 Gy radiation treatment in MCF-7 mammosphere cells (predominantly CD24(-/low)/CD44(+) CICs), but not in the bulk population of MCF-7 cells (predominantly CD24(+)/CD44(+)). Using apoptosis and clonogenic survival assays, we found pharmacological inhibition of AKT with selective inhibitors of AKT sensitized MCF-7 mammosphere cells, but not MCF-7 monolayer cells to radiation. CONCLUSION: The present findings suggest that treatment with AKT inhibitors prior to ionizing radiation treatment may be a potential benefit to patients with breast cancer, in particular to eradiate breast CICs.
Authors: Mercy S Chen; Wendy A Woodward; Fariba Behbod; Sirisha Peddibhotla; Maria P Alfaro; Thomas A Buchholz; Jeffrey M Rosen Journal: J Cell Sci Date: 2007-01-16 Impact factor: 5.285
Authors: Wendy A Woodward; Mercy S Chen; Fariba Behbod; Maria P Alfaro; Thomas A Buchholz; Jeffrey M Rosen Journal: Proc Natl Acad Sci U S A Date: 2007-01-03 Impact factor: 11.205
Authors: Lorena de la Peña; William E Burgan; Donna J Carter; Melinda G Hollingshead; Merriline Satyamitra; Kevin Camphausen; Philip J Tofilon Journal: Mol Cancer Ther Date: 2006-06 Impact factor: 6.261
Authors: Zibin Jiang; Nabendu Pore; George J Cerniglia; Rosemarie Mick; Maria-Magdelena Georgescu; Eric J Bernhard; Stephen M Hahn; Anjali K Gupta; Amit Maity Journal: Cancer Res Date: 2007-05-01 Impact factor: 12.701