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[Cancer Research 59, 1096-1101, March 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 1096-1101, March 1, 1999]
© 1999 American Association for Cancer Research

Molecular Biology and Genetics

G-Protein {gamma} 7 Is Down-Regulated in Cancers and Associated with P 27kip1-induced Growth Arrest

Kohei Shibata, Shinji Tanaka, Takeshi Shiraishi, Seigo Kitano and Masaki Mori1

Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu 874 [K. S., S. T., T. S., M. M.], and Department of Surgery I, Oita Medical University, Oita 875 [S. K.], Japan

We previously identified and cloned human G protein {gamma} 7 (G-{gamma} 7) gene, which is down-regulated in pancreatic cancer. We examined G-{gamma} 7 expression in other gastrointestinal tract cancers. In 24 of 30 patients with gastrointestinal tract cancer, Northern blot assay and immunohistochemical staining revealed significantly lower G-{gamma} 7 expression in tumors than in normal tissues from the same patients. Semiquantitative reverse transcription PCRs also showed lower G-{gamma} 7 expression in tumors than in corresponding normal tissues in 69 of 90 patients. To examine the biological role of G-{gamma} 7 in cancer, the G-{gamma} 7 cDNA was transfected into a human esophageal carcinoma cell line, KYSE150, that lacks G-{gamma} 7 expression. G-{gamma} 7 expression suppressed cell growth and tritiated-thymidine uptake when cells were confluent. G-{gamma} 7 expression also suppressed tumorigenicity in BALB/c nude mice until 3 weeks after transplantation. G-{gamma} 7 expression increased the G0/G1 population and decreased the S phase population when cells were at high density. We confirmed that this change was associated with p27Kip1 expression. These findings suggest that human G-{gamma} 7 is associated with p27kip1-induced growth arrest and may be a therapeutic target in cancers.




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Copyright © 1999 by the American Association for Cancer Research.