Caspase expression profile and functional activity in a panel of breast cancer cell lines.
Caspases play an essential role in the initiation/regulation of apoptosis. Aberrant apoptotic regulation has been associated with carcinogenesis and therapeutic resistance. To explore the possible involvement of altered caspase expression in breast cancer, we have systematically examined the expression of both protein and mRNA levels of 7 caspases in a panel of 18 breast cancer cell lines. We found that variation of caspase expression can occur at both protein and RNA levels. Down-regulation of these caspases, especially caspase-8 and -10, was frequently observed. Functional screening of these selected cell lines using TNF-alpha, doxorubicin and radiation induced cell injury showed that a lack of functional caspase-8 resulted in resistance to TNF-alpha-induced apoptosis. Array style examination of caspase expression profiles in breast cancer cell lines yields massive information that is valuable in establishing cell line models to study the role of caspase down-regulation/deficiency in breast cancer development and therapeutic resistance.
Yang
Shihe
S
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Liu
Joan
J
Thor
Ann D
AD
Yang
Xiaohe
X
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053477:Apoptotic Protease-Activating Factor 1 / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D007527:Isoenzymes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D020169:Caspases