Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets

Abstract

Intracellular lipid accumulation has been associated with a poor prog nosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. In this study, we evaluate the role of lipid droplets in cell cycle regula tion and cellular transformation. Cell cycle synchronization of NIH 3T3 cells revealed increased numbers and dispersed distribution of lipid droplets specifically during S phase. Also, the transformed cell lineage NIH 3T3-H-rasV12 showed an accumulation of both lipid droplets and PLIN2 protein above the levels in NIH 3T3 cells. PLIN2 gene overexpression, however, was not able to induce NIH 3T3 cell transformation, disproving the hypothesis that PLIN2 is an oncogene. Furthermore, positive PLIN2 staining was strongly associated with highly proliferative Ki-67-positive areas in hu man colon adenocarcinoma tissue samples. Taken together, these results indicate that cell cycle progression is associated with tight regulation of lipid droplets, a pro cess that is altered in transformed cells, suggesting the existence of a mechanism that connects cell cycle progression and cell proliferation with lipid accumulation.