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G-protein gamma 7 is down-regulated in cancers and associated with p 27kip1-induced growth arrest
K Shibata1, S Tanaka, T Shiraishi
1Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Abstract:
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 Go/G1 population and decreased the S phase population when cells were at high density. We confirmed that this change was associated with p27K1P1 expression. These findings suggest that human G-gamma 7 is associated with p27kip1-induced growth arrest and may be a therapeutic target in cancers.
Insights
Human G protein gamma 7 (G-gamma 7) is down-regulated in gastrointestinal cancers. Restoring G-gamma 7 expression inhibits cancer cell growth and tumorigenicity, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Human G protein gamma 7 (G-gamma 7) gene was previously identified and found to be down-regulated in pancreatic cancer.
- G-gamma 7 plays a role in cellular processes and its dysregulation is implicated in various diseases.
Purpose of the Study:
- To investigate G-gamma 7 expression levels in various gastrointestinal tract cancers.
- To elucidate the biological role of G-gamma 7 in cancer development and progression.
- To explore G-gamma 7 as a potential therapeutic target for cancer treatment.
Main Methods:
- Northern blot assay and immunohistochemical staining were used to assess G-gamma 7 expression in patient tumor and normal tissues.
- Semiquantitative reverse transcription PCR (RT-PCR) was employed to quantify G-gamma 7 mRNA levels.
- G-gamma 7 cDNA was transfected into a human esophageal carcinoma cell line (KYSE150) to study its functional effects.
- Cell growth, proliferation (tritiated-thymidine uptake), cell cycle distribution, and tumorigenicity in nude mice were evaluated.
- Expression levels of p27Kip1 were analyzed in relation to G-gamma 7 expression.
Main Results:
- Significantly lower G-gamma 7 expression was observed in tumors compared to normal tissues in a majority of gastrointestinal cancer patients (24/30 by Northern blot/immunohistochemistry, 69/90 by RT-PCR).
- G-gamma 7 expression in KYSE150 cells suppressed cell growth, proliferation, and tumorigenicity in vivo.
- G-gamma 7 expression led to an increase in the Go/G1 cell cycle population and a decrease in the S phase population, associated with elevated p27Kip1 expression.
Conclusions:
- Human G-gamma 7 is frequently down-regulated in gastrointestinal cancers.
- G-gamma 7 expression suppresses cancer cell growth and tumorigenicity.
- G-gamma 7-induced growth arrest is linked to p27Kip1, positioning G-gamma 7 as a potential therapeutic target for cancers.