| RRC ID |
38888
|
| 著者 |
Kuda M, Kohashi K, Yamada Y, Maekawa A, Kinoshita Y, Nakatsura T, Iwamoto Y, Taguchi T, Oda Y.
|
| タイトル |
FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target.
|
| ジャーナル |
Tumour Biol
|
| Abstract |
The transcription factor Forkhead box M1 (FOXM1) is known to play critical roles in the development and progression of various types of cancer, but the clinical significance of FOXM1 expression in rhabdomyosarcoma (RMS) is unknown. This study aimed to determine the role of FOXM1 in RMS. We investigated the expression levels of FOXM1 and vascular endothelial growth factor (VEGF) and angiogenesis in a large series of RMS clinical cases using immunohistochemistry (n = 92), and we performed clinicopathologic and prognostic analyses. In vitro studies were conducted to examine the effect of FOXM1 knock-down on VEGF expression, cell proliferation, migration, and invasion in embryonal RMS (ERMS) and alveolar RMS (ARMS) cell lines, using small interference RNA (siRNA). High FOXM1 expression was significantly increased in the cases of ARMS, which has an adverse prognosis compared to ERMS (p = 0.0310). The ERMS patients with high FOXM1 expression (n = 25) had a significantly shorter survival than those with low FOXM1 expression (n = 24; p = 0.0310). FOXM1 expression was statistically correlated with VEGF expression in ERMS at the protein level as shown by immunohistochemistry and at the mRNA level by RT-PCR. The in vitro study demonstrated that VEGF mRNA levels were decreased in the FOXM1 siRNA-transfected ERMS and ARMS cells. FOXM1 knock-down resulted in a significant decrease of cell proliferation and migration in all four RMS cell lines and invasion in three of the four cell lines. Our results indicate that FOXM1 overexpression may be a prognostic factor of RMS and that FOXM1 may be a promising therapeutic target for the inhibition of RMS progression.
|
| 巻・号 |
37(4)
|
| ページ |
5213-23
|
| 公開日 |
2016-4-1
|
| DOI |
10.1007/s13277-015-4351-9
|
| PII |
10.1007/s13277-015-4351-9
|
| PMID |
26553361
|
| MeSH |
Adolescent
Adult
Aged
Aged, 80 and over
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
Child
Child, Preschool
Female
Forkhead Box Protein M1 / biosynthesis*
Forkhead Box Protein M1 / genetics
Gene Expression Regulation, Neoplastic
Humans
Infant
Infant, Newborn
Male
Middle Aged
Neoplasm Invasiveness / genetics
Neovascularization, Pathologic / genetics*
Prognosis
RNA, Messenger / biosynthesis
Rhabdomyosarcoma / genetics*
Rhabdomyosarcoma / pathology
Vascular Endothelial Growth Factor A / genetics*
|
| IF |
3.65
|
| 引用数 |
8
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RMS-YM(RCB1695) |
