| RRC ID |
52373
|
| 著者 |
Kawabata H, Azuma K, Ikeda K, Sugitani I, Kinowaki K, Fujii T, Osaki A, Saeki T, Horie-Inoue K, Inoue S.
|
| タイトル |
TRIM44 Is a Poor Prognostic Factor for Breast Cancer Patients as a Modulator of NF-κB Signaling.
|
| ジャーナル |
Int J Mol Sci
|
| Abstract |
Many of the tripartite motif (TRIM) proteins function as E3 ubiquitin ligases and are assumed to be involved in various events, including oncogenesis. In regard to tripartite motif-containing 44 (TRIM44), which is an atypical TRIM family protein lacking the RING finger domain, its pathophysiological significance in breast cancer remains unknown. We performed an immunohistochemical study of TRIM44 protein in clinical breast cancer tissues from 129 patients. The pathophysiological role of TRIM44 in breast cancer was assessed by modulating TRIM44 expression in MCF-7 and MDA-MB-231 breast cancer cells. TRIM44 strong immunoreactivity was significantly associated with nuclear grade (p = 0.033), distant disease-free survival (p = 0.031) and overall survival (p = 0.027). Multivariate analysis revealed that the TRIM44 status was an independent prognostic factor for distant disease-free survival (p = 0.005) and overall survival (p = 0.002) of patients. siRNA-mediated TRIM44 knockdown significantly decreased the proliferation of MCF-7 and MDA-MB-231 cells and inhibited the migration of MDA-MB-231 cells. Microarray analysis and qRT-PCR showed that TRIM44 knockdown upregulated CDK19 and downregulated MMP1 in MDA-MB-231 cells. Notably, TRIM44 knockdown impaired nuclear factor-kappa B (NF-κB)-mediated transcriptional activity stimulated by tumor necrosis factor α (TNFα). Moreover, TRIM44 knockdown substantially attenuated the TNFα-dependent phosphorylation of the p65 subunit of NF-κB and IκBα in both MCF-7 and MDA-MB-231 cells. TRIM44 would play a role in the progression of breast cancer by promoting cell proliferation and migration, as well as by enhancing NF-κB signaling.
|
| 巻・号 |
18(9)
|
| 公開日 |
2017-9-8
|
| DOI |
10.3390/ijms18091931
|
| PII |
ijms18091931
|
| PMID |
28885545
|
| PMC |
PMC5618580
|
| MeSH |
Adult
Aged
Biomarkers, Tumor
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / mortality*
Breast Neoplasms / pathology
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Immunohistochemistry
Intracellular Signaling Peptides and Proteins
Middle Aged
NF-kappa B / metabolism*
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Prognosis
Protein Binding
Signal Transduction*
Tripartite Motif Proteins
|
| IF |
4.556
|
| 引用数 |
18
|
| リソース情報 |
| ヒト・動物細胞 |
MCF7(RCB1904) |
