| First Author | Loeper S | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 10 | Pages | 3715-23 |
| PubMed ID | 18483254 | Mgi Jnum | J:135021 |
| Mgi Id | MGI:3790262 | Doi | 10.1158/0008-5472.CAN-08-0103 |
| Citation | Loeper S, et al. (2008) Ikaros modulates cholesterol uptake: a link between tumor suppression and differentiation. Cancer Res 68(10):3715-23 |
| abstractText | Ikaros is a transcription factor that directs lymphoid lineage commitment and pituitary neuroendocrine cell expansion and function. Here, we show that Ikaros regulates the low-density lipoprotein receptor (LDL-R) to alter metabolism in pituitary corticotroph cells. The DNA-binding Ikaros isoform Ik1 binds and enhances activity of the LDL-R promoter. Ik1 decreases methylation and increases acetylation of histone H3 (Lys(9)) at the LDL-R promoter. Confocal microscopy and quantitative fluorometry show enhanced LDL endocytosis in Ik1-transfected cells that exhibit abundant endoplasmic reticulum, large Golgi complexes, and prominent secretory granule formation, consistent with more robust cholesterol incorporation into functionally relevant membrane-rich organelles. Consistent with these data, LDL-R(-/-) mice, like Ik(-/-) mice, have decreased circulating levels of adrenocorticotropic hormone. These findings expand the repertoire of Ikaros actions to include regulation of the cholesterol uptake metabolic pathway with therapeutic implications for lipid-modifying drugs in Ikaros-associated cancers. |
