Expression profiling of tumor necrosis factor alpha-induced apoptosis-associated genes in human solid tumor cell lines.
BACKGROUND
The induction of genes associated with cellular apoptosis by tumor necrosis factor-alpha (TNF-alpha) in human cancer cell line sof various tissue origins may characterize TNF-alpha responder cell lines/cancers.


METHODS
Using quantitative real-time polymerase chain reaction (PCR), the comprehensive molecular profiling of genes downstream of the TNF-alpha receptor genes in 91 well-defined human cancer cell lines allowed us to elucidate relationships between TNF-alpha response and the genetic expression profiles of the target cell lines.


RESULTS
Among the 52 genes tested, the above average expression of Akt mRNA showed significant correlation with TNF-alpha-induced susceptibility to apoptosis. In addition, multidrug resistance protein 5 (MRP5) and tumor necrosis factor receptor type 1 (TNFR1) mRNA expressions also appear to be possible markers for responsiveness to TNF-alpha.


CONCLUSIONS
These results provide a preliminary basis for the screening for genetic markers that may help to predict a favorable therapeutic outcome, and also to identify patients who may benefit from cytokine therapy.
Yanai
Yoshiaki
Y
Hayashibara Biochemical Laboratories Inc., Fujisaki Institute, Fujisaki 675-1, Okayama 702-8006, Japan.
Micallef
Mark J
MJ
Yamamoto
Shigeto
S
Yamamoto
Kozou
K
Yamauchi
Hiroshi
H
Ikegami
Hakuo
H
Kurimoto
Masashi
M
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018799:Intercellular Adhesion Molecule-1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C120809:ABCC5 protein, human; C494918:AKT1 protein, human