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Reversible effect of all-trans-retinoic acid on AML12 hepatocyte proliferation and cell cycle progression
Citation:
MURPHY, L. A., T. MOORE, AND S. NESNOW. Reversible effect of all-trans-retinoic acid on AML12 hepatocyte proliferation and cell cycle progression. Presented at American Association for Cancer Research (AACR) Annual Meeting, Washington, DC, April 17 - 21, 2010.
Impact/Purpose:
Using AML12 cells, a non-transformed immortalized mouse hepatocyte cell line, the goals of this study were to first determine if changes in AML12 cell proliferation could be observed in response to atRA treatment and establish whether this was a suitable system to investigate molecular mechanisms altered by the hepatocarcinogens.
Description:
The role of all-trans-retinoic acid (atRA) in the regulation of cellular proliferation and differentiation is well documented. Numerous studies have established the cancer preventive propertiesofatRAwhichfunctionstoregulate levels ofcellcycleproteinsessentialfortheGliS transition and progression through S phase. Using AML12 cells, a non-transformed immortalized mouse hepatocyte cell line, the goals of this study were to first determine if changes in AML12 cell proliferation could be observed in response to atRA treatment and establish whether this was a suitable system to investigate molecular mechanisms altered by the hepatocarcinogens. Cells were treated with 111M and 5 11M atRA for 2 to 10 days. At various time points, control (DMSO) and treated cells were enumerated to determine the effect of atRA on AML12 cell proliferation. At 5 days of atRA treatment, there was a 56% decrease in the number of atRA treated cells when compared to control cells. This effect was reversible as an increase in cell number was observed two days after removal of atRA from the treatment media. Cell cycle analysis by flow cytometry using propidium iodide stained AML12 cells showed a significant reduction (p