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Preneoplastic alterations in nuclear morphology that accompany loss of tumor suppressor phenotype
J Boyd1, K J Pienta, R H Getzenberg
1Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Abstract:
Alterations of nuclear shape are frequently observed in tumor cells, but the genes controlling these changes and the stage in the neoplastic process at which they occur are unknown. We have studied nuclear shape changes in chemically immortalized, nontumorigenic Syrian hamster embryo cell clones that had either retained (supB+) or lost (supB-) the ability to suppress the tumorigenic phenotype when they were hybridized with a tumor cell line (BP6T). Quantitative morphometric analysis of the nuclei of cells from each of two pairs of supB+/supB- variants indicated that the nuclei of supB- cells were significantly more out of round than those of their corresponding supB+ clones. These data indicate that modification of nuclear structure may represent an early, preneoplastic event in multistep chemical carcinogenesis and that loss of a tumor suppressor gene function may regulate alterations in nuclear morphology.
Insights
Altered nuclear shape in cells may signal early cancer development. Loss of tumor suppressor gene function appears to control these preneoplastic nuclear changes.
Area of Science:
- Cell biology
- Cancer research
- Genetics
Background:
- Nuclear shape alterations are common in tumor cells, but the underlying genes and timing are unclear.
- Understanding these changes is crucial for identifying early neoplastic events.
Purpose of the Study:
- To investigate the relationship between nuclear shape and tumor suppressor gene function.
- To determine if nuclear morphology changes occur early in chemical carcinogenesis.
Main Methods:
- Studied chemically immortalized Syrian hamster embryo cell clones with retained (supB+) or lost (supB-) tumor suppressor gene function.
- Utilized quantitative morphometric analysis to assess nuclear shape in supB+ and supB- cell variants.
Main Results:
- supB- cells exhibited significantly more irregular nuclear shapes compared to their supB+ counterparts.
- Nuclear shape modification was observed even in non-tumorigenic cells that had lost suppressor function.
Conclusions:
- Modification of nuclear structure may be an early, preneoplastic event in chemical carcinogenesis.
- Loss of tumor suppressor gene function appears to regulate alterations in nuclear morphology, suggesting a role in early cancer development.