| RRC ID |
51685
|
| 著者 |
Li W, Itou J, Tanaka S, Nishimura T, Sato F, Toi M.
|
| タイトル |
A homeobox protein, NKX6.1, up-regulates interleukin-6 expression for cell growth in basal-like breast cancer cells.
|
| ジャーナル |
Exp Cell Res
|
| Abstract |
Among breast cancer subtypes, basal-like breast cancer is particularly aggressive, and research on the molecules involved in its pathology might contribute to therapy. In this study, we found that expression of NKX6.1, a homeobox transcription factor, is higher in basal-like breast cancer than in other subtypes. In loss-of-function experiments on basal-like breast cancer cell lines, NKX6.1-depleted cells exhibited reduced cell growth. Because cytokine interleukin-6 (IL-6) is expressed in basal-like breast cancer, and increases cell growth, we analyzed expression levels of IL6, an IL-6 gene, and observed reduced IL6 expression in NKX6.1-depleted cells. In a reporter assay, IL6 promoter activity was reduced by loss of NKX6.1 function. A pull-down assay showed that NKX6.1 binds to the proximal region in IL6 promoter. These results indicate that NKX6.1 directly up-regulates IL6 expression. To investigate further, we established cells with forced expression of IL-6. We observed that exogenous IL-6 expression restored the reduced cell growth of NKX6.1-depleted cells. Furthermore, orthotopic xenografts showed that NKX6.1-depleted cells lost the capacity for tumor formation. We therefore conclude that NKX6.1 is a factor for IL-6-regulated growth and tumor formation in basal-like breast cancer. Our findings facilitate profound understanding of basal-like breast cancer, and the development of suitable therapy.
|
| 巻・号 |
343(2)
|
| ページ |
177-189
|
| 公開日 |
2016-5-1
|
| DOI |
10.1016/j.yexcr.2016.03.023
|
| PII |
S0014-4827(16)30063-5
|
| PMID |
27032575
|
| MeSH |
Animals
Base Sequence
Breast Neoplasms / genetics*
Breast Neoplasms / pathology*
Carcinogenesis / pathology
Cell Line, Tumor
Cell Proliferation
Feedback, Physiological
Female
Gene Expression Regulation, Neoplastic*
Homeodomain Proteins / metabolism*
Humans
Interleukin-6 / genetics*
Interleukin-6 / metabolism
Mice, Inbred NOD
Mice, SCID
Models, Biological
Promoter Regions, Genetic
Up-Regulation / genetics*
|
| IF |
3.383
|
| 引用数 |
4
|
| リソース情報 |
| ヒト・動物細胞 |
LoVo(RCB1639)
HCT116(RCB2979) |
