STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells.
Signal transduction and activator of transcription 3(STAT3) signaling is constitutively activated in various tumors, and is involved in cell survival and proliferation during oncogenesis. There are few reports, however, on the role of STAT3 signaling in gastric cancer. The aim of the present study was to clarify the role of STAT3 signaling in apoptosis and cellular proliferation in gastric cancer. Here we reported that STAT3 was constitutively activated in various human gastric cancer cells and its inhibition by ectopic dominant-negative STAT3 or Janus kinase inhibitor, tyrphostin AG490, induced apoptosis. Furthermore, STAT3 inhibition markedly decreased survivin expression, and forced expression of survivin rescued AGS cells from apoptosis induced by STAT3 inhibition. Although some reports demonstrated that the PI3K/Akt pathway regulates survivin expression, inhibition of the PI3K/Akt pathway did not affect survivin expression in AGS and MKN1 cells. Finally, activated form of STAT3, Tyr-705 phospho-stat3, was found in the nucleus of cancer cells in 11 of 40 (27.5%) human gastric cancer specimens. These findings suggest that constitutively activated STAT3 signaling supports gastric cancer cell survival in association with survivin expression.2004
Kanda
Naoki
N
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Shogoin-Kawara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan.
Seno
Hiroshi
H
Konda
Yoshitaka
Y
Marusawa
Hiroyuki
H
Kanai
Masashi
M
Nakajima
Toshio
T
Kawashima
Tomoko
T
Nanakin
Apichart
A
Sawabu
Tateo
T
Uenoyama
Yoshito
Y
Sekikawa
Akira
A
Kawada
Mayumi
M
Suzuki
Katsumasa
K
Kayahara
Takahisa
T
Fukui
Hirokazu
H
Sawada
Mitsutaka
M
Chiba
Tsutomu
T
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics; D002470:Cell Survival / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013274:Stomach Neoplasms; D000077022:Survivin; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
D000209:Acute-Phase Proteins; C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D015534:Trans-Activators