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Similarities between somatic cells overexpressing the mos oncogene and oocytes during meiotic interphase
K Fukasawa1, M S Murakami, D G Blair
1ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201.
Abstract:
The mos protooncogene encodes a serine/threonine kinase and is a key regulator of oocyte meiotic maturation. After acute infection of Swiss 3T3 cells with virus containing the v-mos oncogene, cells expressing high levels of v-Mos round up and detach from the monolayer (floating cells), while cells that remain attached express 10-fold lower levels of v-Mos and are transformed. The floating cells are growth arrested with their chromosomes partially condensed in the absence of histone H1 kinase activity, while mitogen-activated protein kinase activity is very high. Collectively, these properties are similar to properties observed in maturing oocytes between meiosis I and II. In v-mos-transformed cell populations, mitogen-activated protein kinase activity is also elevated, correlating with the degree of morphological transformation and the level of Mos expression. Moreover, phosphoprotein modifications specific for M are found in both the floating cells and in v-mos-transformed cells, regardless of their cell cycle stage. One explanation for both morphological transformation and the phenotypes of the floating cells is that Mos imposes a meiotic program on different stages of the somatic cell cycle. The extent of this meiotic phenotype is proportional to the level of v-Mos expression. These results suggest that both morphological transformation and the phenotypes of the floating cells induced by Mos in Swiss 3T3 cells are related to its normal activities during oocyte maturation.
Insights
The mos protooncogene, a regulator of oocyte maturation, induces meiotic phenotypes in somatic cells. Elevated v-Mos expression drives cell rounding and transformation by imposing a meiotic program.
Area of Science:
- Cell Biology
- Molecular Oncology
- Developmental Biology
Background:
- The mos protooncogene encodes a serine/threonine kinase crucial for oocyte meiotic maturation.
- Understanding Mos's function in somatic cells can elucidate its role in oocyte development.
Purpose of the Study:
- To investigate the effects of v-mos oncogene expression in Swiss 3T3 cells.
- To determine if Mos imposes a meiotic program on somatic cells.
Main Methods:
- Acute infection of Swiss 3T3 cells with a virus containing the v-mos oncogene.
- Analysis of cell morphology, growth, chromosome condensation, and kinase activity (histone H1 and mitogen-activated protein kinase).
- Detection of Mos-specific phosphoprotein modifications.
Main Results:
- High v-Mos expression caused cells to round up and detach (floating cells), exhibiting growth arrest and high mitogen-activated protein kinase activity.
- Low v-Mos expression in attached cells led to transformation.
- Both floating and transformed cells displayed Mos-specific phosphoprotein modifications, irrespective of cell cycle stage.
- The observed phenotypes mimicked oocyte maturation between meiosis I and II.
Conclusions:
- Mos imposes a meiotic program on somatic cells, with the extent proportional to v-Mos expression.
- The morphological transformation and floating cell phenotypes are linked to Mos's normal functions during oocyte maturation.