Endogenous tumor necrosis factor promotes resistance to cellular stresses by inducing the metallothionein-1A gene.
BACKGROUND
Endogenous tumor necrosis factor (enTNF) acts as a resistance factor against anticancer drugs, heat and exogenous TNF via induction of manganous superoxide dismutase (MnSOD) and heat shock protein 72 (HSP72), while the details of interaction with other molecules are not fully understood. We compared mRNA expression of various genes between MIAPaCa-2 human pancreatic cancer cells and M5 cells transduced with nonsecretory-type TNF gene expression vector.


METHODS
The expression of certain mRNAs between human pancreatic cancer MIAPaCa-2 cells and M5 cells was compared using fluorescent differential display.


RESULTS
Of 140 bands obtained by gel electrophoresis, 53 bands showed patterns differing between MIAPaCa-2 and M5 cells. Among these bands, sequence analysis and RT-PCR identified strong mRNA expression for metallothionein-1A, a scavenger of reactive oxygen species, in transduced M5 cells.


CONCLUSIONS
Metallothionein-1A could be induced by enTNF, resulting in resistance against various cellular stresses.
Hadama
Tohru
T
Gene Analysis Center, Otsuka Assay Laboratories, Otsuka Life Science Initiative, Otsuka Pharmaceutical Co., Ltd., 463-1, Kagasuno, Kawauchicyo, Tokushima 771-0129, Japan.
Kinoshita
Moritoshi
M
Kobayashi
Daisuke
D
Tsuji
Naoki
N
Watanabe
Naoki
N
D001483:Base Sequence; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008668:Metallothionein