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myc family gene abnormality in lung cancers and its relation to xenotransplantability
A Gemma1, T Nakajima, M Shiraishi
1Pathology, Division National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
In order to study the relationship between tumor transplantability to the nude mouse and abnormality of the myc family genes (c-myc, N-myc, L-myc) in human primary lung cancers, 32 various lung cancers were analyzed for abnormality of the myc family genes by Southern blot hybridization, and were transplanted s.c. into nude mice. Southern blot analysis showed that four non-small cell carcinomas and three small cell carcinomas had amplified c-myc and L-myc genes, respectively. Allelic deletion of the L-myc gene was observed in seven cancers, of which two also had an additional band of the c-myc gene or amplification of the L-myc gene. No abnormality of the N-myc gene was observed in this series. Of 13 cancers with abnormality of the myc family genes, 11, including all tumors with myc gene amplification, were transplantable to nude mice. Of 19 tumors without any abnormalities of the myc family genes, however, only five were transplantable to nude mice (P less than 0.005). These results indicate that abnormality of the myc family genes, especially gene amplification, might promote tumorigenic ability in xenotransplantation of lung cancers and this phenomenon might be closely related to the function of the myc gene.
Insights
Abnormalities in myc family genes, particularly gene amplification, enhance the tumor transplantability of human lung cancers in nude mice. These findings suggest myc gene alterations promote xenotransplantation tumorigenic ability.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The myc gene family (c-myc, N-myc, L-myc) plays a crucial role in cell growth and differentiation.
- Alterations in myc family genes are frequently observed in various cancers, including lung cancer.
Purpose of the Study:
- To investigate the correlation between the transplantability of human primary lung cancers in nude mice and abnormalities in the myc family genes.
- To determine if myc gene alterations influence the tumorigenic potential of lung cancer xenografts.
Main Methods:
- Analysis of 32 human primary lung cancers for myc family gene abnormalities (c-myc, N-myc, L-myc) using Southern blot hybridization.
- Subcutaneous transplantation of these lung cancer samples into nude mice to assess tumor growth and transplantability.
Main Results:
- Myc family gene abnormalities, including amplification of c-myc and L-myc, were detected in 13 of 32 lung cancers.
- Tumors with myc gene abnormalities, especially gene amplification, showed significantly higher transplantability rates in nude mice compared to those without abnormalities (11/13 vs. 5/19, P < 0.005).
- No N-myc gene abnormalities were observed in this study cohort.
Conclusions:
- Abnormalities in myc family genes, particularly amplification, are associated with enhanced tumorigenic ability in lung cancer xenotransplantation models.
- These findings suggest that myc gene alterations may promote the growth and survival of lung cancer cells in vivo, contributing to their transplantability.
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