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Different expression patterns of oncogenes and proto-oncogenes in hereditary and carcinogen-induced tumors of
W Mäueler1, A Schartl, M Schartl
1Max-Planck-Institut für Biochemie, Martinsried bei München, Germany.
Abstract:
Hereditary melanoma in Xiphophorus hybrids carrying the melanoma-inducing Tu-Sd locus is caused by transcriptional activation of the Xmrk gene that resides at the Tu-Sd locus and encodes a novel member of receptor tyrosine kinases (RTK). In this study, a total of 27 hereditary melanomas from various hybrid genotypes harbouring 7 different Tu alleles were also found to over-express the corresponding Xmrk alleles. The level of over-expression correlated with the degree of malignancy of the melanoma. In addition, Xsrc expression was high in many malignant melanomas. Expression patterns and levels of the Xiphophorus EGF-receptor gene (Xerb B), the c-myc (Xmyc), and the PDGF (Xsis) gene(s) were not intriguing. Transcription of the ras gene(s) may be correlated to secondary events of melanoma progression. Expression patterns of Xfms, the Xiphophorus CSF-I receptor homologue, can be explained by different contents of infiltrating macrophages in the tumors. In carcinogen-induced tumors including one melanoma no significant expression of the Xmrk oncogene could be detected. Xsrc expression, however, was strikingly high. This indicates that activation of oncogenes other than Xmrk is instrumental in tumorigenesis of neoplasia of non-hereditary origin.
Insights
Hereditary melanoma in Xiphophorus fish is linked to over-expression of the Xmrk receptor tyrosine kinase (RTK) oncogene. Non-hereditary melanomas show high Xsrc expression, suggesting alternative oncogene activation in tumor development.
Area of Science:
- Genetics
- Oncology
- Developmental Biology
Background:
- Hereditary melanoma in Xiphophorus fish arises from the Tu-Sd locus.
- This locus contains the Xmrk gene, encoding a novel receptor tyrosine kinase (RTK).
Purpose of the Study:
- Investigate the role of Xmrk gene over-expression in hereditary melanoma.
- Analyze oncogene expression in both hereditary and carcinogen-induced melanomas.
- Determine the correlation between oncogene expression levels and melanoma malignancy.
Main Methods:
- Analysis of Xmrk gene expression in 27 hereditary melanomas from Xiphophorus hybrids.
- Quantification of Xmrk allele over-expression and correlation with melanoma malignancy.
- Assessment of Xsrc, Xerb B, Xmyc, Xsis, Xfms, and ras gene expression patterns.
Main Results:
- Over-expression of Xmrk alleles was observed in all hereditary melanomas studied.
- Higher Xmrk over-expression correlated with increased melanoma malignancy.
- Xsrc expression was high in malignant melanomas, and significantly elevated in carcinogen-induced melanomas.
- Expression of Xerb B, Xmyc, Xsis, and Xfms showed less significant correlations with melanoma progression.
Conclusions:
- Transcriptional activation of Xmrk is the primary driver of hereditary melanoma in Xiphophorus.
- Activation of oncogenes other than Xmrk, such as Xsrc, is crucial for non-hereditary melanoma development.
- Oncogene expression patterns provide insights into the distinct mechanisms of hereditary versus induced tumorigenesis.