Loss of putative tumor suppressor EI24/PIG8 confers resistance to etoposide.
Expression of p53-target gene EI24/PIG8 is lost in invasive breast cancers, suggesting that EI24/PIG8 is a tumor suppressor that prevents tumor spreading, and partially mediates p53-attributed tumor suppressor activity. EI24/PIG8 also has pro-apoptotic activity indicating that loss of EI24/PIG8 may modulate sensitivity to chemotherapy. Here it is demonstrated that suppression of EI24/PIG8 in fibroblasts and breast cancer cells significantly inhibits the apoptotic response to etoposide treatment. These findings suggest that loss of EI24/PIG8 contributes significantly to resistance of cells to chemotherapeutic agents that function through p53, and identify the EI24/PIG8 status as a potentially new prognostic marker of chemotherapy responsiveness.
Mork
Christina N
CN
Department of Microbiology, Cancer Research Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Faller
Douglas V
DV
Spanjaard
Remco A
RA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004351:Drug Resistance / Q000187:drug effects*; D005047:Etoposide / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C402592:EI24 protein, human; C526185:EI24 protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D005047:Etoposide