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GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development
S Sabbioni1, G Barbanti-Brodano, C M Croce
1Department of Experimental and Diagnostic Medicine and Interdepartment Center for Biotechnology, University of Ferrara, Italy.
Abstract:
The expression of GOK, a gene recently identified at 11p15.5, was studied in breast cancer, rhabdomyosarcoma, and rhabdoid tumor cell lines. In these neoplasms, deletions at 11p15 and suppression of tumorigenicity induced by a normal human chromosome 11 were previously demonstrated. Whereas breast cancer cell lines express readily detectable levels of GOK mRNA, expression is absent in rhabdomyosarcoma and rhabdoid tumor cell lines. This is in contrast with the high expression of GOK in skeletal muscle, the normal tissue of origin of rhabdomyosarcomas, suggesting that down-regulation of GOK expression could be involved in tumor development. In agreement with this hypothesis, transfection of GOK cDNA into G401 derived from a rhabdoid tumor and RD cells derived from a rhabdomyosarcoma that do not express detectable levels of GOK mRNA, induced cell death. Because GOK expression is not compatible with growth of these tumor cells, these results support the hypothesis that loss of GOK expression plays a role in tumor establishment or progression and suggest that GOK may act as a recessive tumor suppressor gene in rhabdomyosarcomas and rhabdoid tumors. On the contrary, transfection of GOK cDNA into the breast cancer cell line HBL100 produced no detectable effects, indicating that the growth-suppressive effect of GOK in RD and G401 cells was specific. Because rhabdomyosarcomas have been observed in cases of Beckwith-Wiedemann syndrome, a genetic disorder linked to 11p15, a role of GOK in this disease cannot be excluded.
Insights
The GOK gene, normally expressed in muscle, is absent in rhabdomyosarcoma and rhabdoid tumors. Restoring GOK expression caused cell death, suggesting it acts as a tumor suppressor gene in these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The GOK gene at 11p15.5 is implicated in tumor development.
- Deletions at 11p15 and chromosome 11-induced suppression of tumorigenicity are known in certain cancers.
- GOK expression patterns were previously uncharacterized in specific tumor types.
Purpose of the Study:
- To investigate the expression of the GOK gene in breast cancer, rhabdomyosarcoma, and rhabdoid tumor cell lines.
- To determine the functional role of GOK in tumor cell growth and survival.
- To explore the potential of GOK as a tumor suppressor gene.
Main Methods:
- Studied GOK gene expression (mRNA levels) in various cancer cell lines.
- Transfected GOK cDNA into tumor cells lacking endogenous expression.
- Observed the effects of GOK reintroduction on cell viability and growth.
Main Results:
- GOK mRNA was detected in breast cancer cell lines but absent in rhabdomyosarcoma and rhabdoid tumor cell lines.
- High GOK expression in skeletal muscle contrasts with its absence in these tumor types.
- Transfection of GOK cDNA into rhabdomyosarcoma and rhabdoid tumor cells induced cell death, indicating a growth-suppressive effect.
- GOK reintroduction had no effect on breast cancer cell lines, suggesting specificity.
Conclusions:
- Loss of GOK expression may contribute to the development or progression of rhabdomyosarcomas and rhabdoid tumors.
- GOK likely functions as a recessive tumor suppressor gene in these specific neoplasms.
- The findings suggest a potential role for GOK in Beckwith-Wiedemann syndrome, given its association with 11p15.