STAT3 and MAPK in human lung cancer tissues and suppression of oncogenic growth by JAB and dominant negative STAT3.
To search for the signaling events in lung carcinoma relevant to its tumorigenesis, we investigated the phosphorylation of MAPK and STAT3 in human lung carcinoma tissues and their paired normal tissues. Although relative amounts of MAPK levels differed among the cases examined, no clear difference in MAPK levels was observed between tumor tissues and their paired normal tissues. Of 79 cases examined, only 7 cases (8.9%) showed tumor-specific phosphorylation of MAPK, whereas 41 cases (52%) showed more than 2-fold lower levels of MAPK phosphorylation in tumor tissues. In contrast to MAPK, 42 cases (53%) showed tumor-specific increase in STAT3 expression. In addition, 15 cases (19%) showed tumor-specific increase of STAT3 phosphorylation and 51 cases (65%) had STAT3 phosphorylation proportional to its expression. Moreover, exogenous expression of either JAB or dominant negative STAT3 in lung carcinoma cell lines led to the suppression of STAT3 phosphorylation and the drastic reduction of anchorage- independent growth of the cells. Taken together, our results suggest that JAK-STAT3 signaling has a pivotal role for oncogenic growth of lung carcinoma cells.
Seki
Yukio
Y
Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Suzuki
Noriko
N
Imaizumi
Munehisa
M
Iwamoto
Takashi
T
Usami
Noriyasu
N
Ueda
Yuichi
Y
Hamaguchi
Michinari
M
D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005799:Genes, Dominant; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases