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[Analysis of c-onc genes in choriocarcinoma cells]
1Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Sapporo, Japan.
Abstract:
Regulatory or structural alterations of c-onc genes including amplification, rearrangement and point mutation was implicated in the causation of various malignant tumors. However, such changes of molecular levels have not been reported so far in choriocarcinoma cells. In the present study, thus, 5 choriocarcinoma cell lines were analyzed by hybridization using 16 oncogene probes. By Southern blot hybridization of DNA extracted from these cells, 8 fold amplification of c-myc gene and rearrangement of c-fms gene were shown in ENAMI cells, although the role of these alterations remained unknown. Northern blot hybridization performed simultaneously demonstrated multiple expression of c-onc genes. 4 choriocarcinoma cell lines (HCCM, CHl, CCl, ENAMI) expressed at least 11 c-onc genes (H-ras, K-ras, N-ras, c-myc, N-myc, fos, fms, src, yes, erb B and raf); though the degree of expression of H-ras, C-myc, erb B and fms in these cells was either similar or enhanced as compared with normal fibroblast, the expression of two c-onc genes (N-myc and fos) was extremely enhanced. However, expression of K-ras and myb was either low or not detected. The multiple expression of c-onc genes seems to reflect partly on growth advantages of trophoblast. Transfection assay using NIH3T3 cells failed to form any transformed foci. Since choriocarcinoma cells which derived from the transformation of trophoblast of complete mole possess the genetic characteristics identical to the one of cells of complete mole, chromosomal instability was assumed to play a major role for multiple oncogene expression in choriocarcinoma cells.
Insights
Choriocarcinoma cells show multiple oncogene expression, including amplified c-myc and rearranged c-fms genes. This suggests chromosomal instability may drive oncogene activity in these cancer cells.
Area of Science:
- Molecular oncology
- Cancer genetics
- Gene regulation
Context:
- Oncogene alterations are linked to various cancers, but not previously reported in choriocarcinoma.
- Choriocarcinoma arises from trophoblast transformation, suggesting a potential link to genetic changes.
Purpose:
- To investigate oncogene alterations and expression patterns in choriocarcinoma cell lines.
- To explore the molecular basis of choriocarcinoma development.
Summary:
- Analysis of 5 choriocarcinoma cell lines revealed 8-fold c-myc amplification and c-fms rearrangement in ENAMI cells.
- Multiple c-onc genes (H-ras, K-ras, N-ras, c-myc, N-myc, fos, fms, src, yes, erb B, raf) were expressed, with N-myc and fos showing extreme enhancement.
- Chromosomal instability is hypothesized as the primary driver for multiple oncogene expression in choriocarcinoma.
Impact:
- Identifies specific oncogene alterations (c-myc, c-fms) and expression profiles in choriocarcinoma.
- Provides insights into the genetic landscape of choriocarcinoma, potentially aiding diagnostic and therapeutic strategies.
- Highlights the role of chromosomal instability in oncogene dysregulation in this cancer type.