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Activation of the receptor kinase domain of the trk oncogene by recombination with two different cellular sequences
S C Kozma1, S M Redmond, X C Fu
1Ludwig Institute for Cancer Research, Bern Branch, Inselspital, Switzerland.
Abstract:
A new chimeric oncogene, trk-2h, has been generated by recombination of two segments of MDA-MB231 human breast carcinoma cell line DNA after transfection in NIH/3T3 cells. The rearranged DNA segments form a fused transcriptional unit. Sequences at the 3' end are homologous to the tyrosine kinase receptor moiety found in the trk oncogene which resembles a truncated growth factor receptor lacking part of its extracellular domain (Martin-Zanca et al., 1986). The 5' sequence of the trk-2h oncogene is contributed by a gene which is expressed in all human cells tested, and is not related to any known gene. Transfection of the receptor kinase domain DNA fragment into NIH/3T3 cells generated another oncogene, trk-3mh, which contains a mouse-specific sequence fused 5' to the receptor kinase. All three trk recombinants have the receptor kinase moiety fused to an activating amino terminus at the same nucleotide in their transcriptional product.
Insights
Researchers created a new chimeric oncogene, trk-2h, by combining DNA segments from human breast cancer cells. This oncogene contains a tyrosine kinase receptor fused to a novel gene sequence, potentially driving cancer development.
Area of Science:
- * Molecular Biology
- * Oncology
- * Genetics
Background:
- * Chimeric oncogenes play a crucial role in cancer development.
- * The trk oncogene encodes a tyrosine kinase receptor implicated in cell growth.
- * Understanding oncogene formation is key to developing targeted cancer therapies.
Purpose of the Study:
- * To characterize a newly generated chimeric oncogene, trk-2h.
- * To investigate the genetic origins and structure of trk-2h.
- * To explore the potential oncogenic activity of novel gene fusions.
Main Methods:
- * Recombination of DNA segments from MDA-MB231 human breast carcinoma cells.
- * Transfection of rearranged DNA into NIH/3T3 cells.
- * Analysis of fused transcriptional units and sequence homology.
Main Results:
- * A novel chimeric oncogene, trk-2h, was successfully generated.
- * trk-2h comprises a tyrosine kinase receptor moiety fused to a previously unidentified human gene sequence.
- * A second oncogene, trk-3mh, was created using a mouse-specific sequence.
Conclusions:
- * The study successfully generated and characterized novel chimeric oncogenes, trk-2h and trk-3mh.
- * These oncogenes feature a common receptor kinase domain fused to different amino-terminal sequences.
- * The findings contribute to understanding oncogene formation and potential therapeutic targets in cancer.