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Ikaros modulates cholesterol uptake: a link between tumor suppression and differentiation
- Source :
- Cancer research. 68(10)
- Publication Year :
- 2008
-
Abstract
- 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 (Lys9) 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. [Cancer Res 2008;68(10):3715–23]
- Subjects :
- Male
Cancer Research
medicine.medical_specialty
Cellular differentiation
Golgi Apparatus
Mice, Transgenic
Biology
Endocytosis
Histone H3
symbols.namesake
Ikaros Transcription Factor
Mice
Adrenocorticotropic Hormone
Internal medicine
Neoplasms
medicine
Animals
Humans
Cell Lineage
Receptor
Transcription factor
Endoplasmic reticulum
Cell Differentiation
Golgi apparatus
Cell biology
Endocrinology
Cholesterol
Oncology
Receptors, LDL
symbols
lipids (amino acids, peptides, and proteins)
Female
Corticotropic cell
Subjects
Details
- ISSN :
- 15387445
- Volume :
- 68
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....e2a30674c56ad8695bd0af878c9110ee