| RRC ID |
67255
|
| 著者 |
Kaneko T, Kanno C, Ichikawa-Tomikawa N, Kashiwagi K, Yaginuma N, Ohkoshi C, Tanaka M, Sugino T, Imura T, Hasegawa H, Chiba H.
|
| タイトル |
Liver X receptor reduces proliferation of human oral cancer cells by promoting cholesterol efflux via up-regulation of ABCA1 expression.
|
| ジャーナル |
Oncotarget
|
| Abstract |
Liver X receptors (LXRs) contribute not only to maintain cholesterol homeostasis but also to control cell growth. However, the molecular mechanisms behind the LXR-mediated anti-proliferative effects are largely unknown. Here we show, by immunohistochemistry, that LXRα and LXRβ are differentially distributed in oral stratified squamous epithelia. By immunohistochemical and Western blot analyses, we also reveal that LXRα is abundantly expressed in human oral squamous cell carcinoma (HOSCC) tissues and cell lines. Cell counting, BrdU labeling and cell cycle assay indicated that LXR stimulation led to significant reduction of proliferation in HOSCC cells. Importantly, our study highlights, by using RNA interference, that the ATP-binding cassette transporter A1 (ABCA1)-accelerated cholesterol efflux is critical for the growth inhibitory action of LXRs in HOSCC cells. Moreover, we demonstrate that LXR activation reduces the growth of xenograft tumour of HOSCC cells in mice accompanied by the upregulation of ABCA1 expression and the decline of cholesterol levels in the tumour. These findings strongly suggested that targeting the LXR-regulated cholesterol transport, yielding in lowering intracellular cholesterol levels, could be a promising therapeutic option for certain types of cancers.
|
| 巻・号 |
6(32)
|
| ページ |
33345-57
|
| 公開日 |
2015-10-20
|
| DOI |
10.18632/oncotarget.5428
|
| PII |
5428
|
| PMID |
26452260
|
| PMC |
PMC4741770
|
| MeSH |
ATP Binding Cassette Transporter 1 / genetics*
ATP Binding Cassette Transporter 1 / metabolism
Adult
Animals
Biological Transport / genetics
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology*
Cell Line, Tumor
Cell Proliferation / genetics*
Cholesterol / metabolism*
Female
Gene Expression Regulation, Neoplastic
HEK293 Cells
Humans
Liver X Receptors
Male
Mice
Mice, SCID
Mouth Neoplasms / genetics
Mouth Neoplasms / metabolism
Mouth Neoplasms / pathology*
Orphan Nuclear Receptors / physiology*
Rats
Rats, Wistar
Up-Regulation / genetics
|
| IF |
5.168
|
| リソース情報 |
| ヒト・動物細胞 |
SAS(RCB1974)
HSC-4(RCB1902)
HO-1-u-1(RCB2102) |
