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- W2059179621 abstract "Abstract Although functional roles have been assigned to many genes, e.g. those involved in cell‐cycle regulation, growth signaling, or cancer, considerably less is known about the quantitative relationship between gene expression levels and outcome. We devised an intra‐population competition to study oncogene dosage. Cell populations were engineered to express a range of H‐Ras oncogene levels. Cells with different levels of H‐Ras then “competed” for an increased share of the total cell population. Using flow cytometry to track the population composition over time, we determined the relationship between the different H‐Ras oncogene expression levels and the net proliferation rate. Under culture conditions in which wild‐type Ras activation was suppressed, we found that increased and maximal net proliferation occurred when the H‐Ras G12V oncogene was expressed at a level 1.2‐fold that of wild‐type Ras. As the H‐Ras G12V expression levels increased above this optimal level, proliferation rates decreased. Our findings suggest that the tumor evolution process may optimize gene expression levels for maximal cell proliferation. In principle, engineered intra‐population competitions can be used to determine proliferation rates associated with the level of any ectopically expressed gene. The approach also may be used to determine proliferation rates associated with different cell species in a heterogeneous population or to improve the proliferation rate of a cell line. We also envision that the tracking of intra‐population competitions could be utilized to investigate the evolution of tumors in the body." @default.
- W2059179621 created "2016-06-24" @default.
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- W2059179621 date "2013-08-05" @default.
- W2059179621 modified "2023-10-04" @default.
- W2059179621 title "Optimization of oncogene expression through intra‐population competition" @default.
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- W2059179621 doi "https://doi.org/10.1002/biot.201300037" @default.
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