A rat mammary tumor cell line maintained in low serum (1%) medium exhibited a slower growth rate, altered cell cycle distribution, decreased DNA synthesis, and increased immunoprecipitable p53, when compared with culture in 10% serum. Addition of linoleic acid (LA; 18:2, n-6) to low serum medium partially restored normal cell cycle distribution, increased synthesis of DNA, and decreased immunoprecipitable p53 to levels normally seen in cells cultured in 10% serum. In contrast, exposure of the cells to docosahexaenoic acid (DHA, 22:6, n-6) induced further suppression of cell proliferation in medium containing 1% serum, and up-regulated expression of p53. The inverse correlation between p53 levels and cell proliferation is consistent with a role for p53 in negative regulation of growth of these tumor cells. The data suggest that growth stimulation of rat mammary tumor cells by LA is mediated in part through modulation of p53 expression.

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