High-density lipoprotein is a potential growth factor for adrenocortical cells.
The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [(3)H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor.
Murao
Koji
K
Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-cho, Kita-gun, Kagawa, Japan. mkoji@kms.ac.jp
Imachi
Hitomi
H
Cao
Wenming
W
Yu
Xiao
X
Li
Junhua
J
Yoshida
Kazuya
K
Ahmed
Rania A M
RA
Matsumoto
Kensuke
K
Nishiuchi
Takamasa
T
Wong
Norman C W
NC
Ishida
Toshihiko
T
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006133:Growth Substances / Q000378:metabolism / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D006133:Growth Substances; D008075:Lipoproteins, HDL; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D051122:Scavenger Receptors, Class B; D018808:Transcription Factor AP-1; D000077191:Wortmannin; C454739:Scarb1 protein, mouse