| RRC ID |
85729
|
| 著者 |
Goto H, Kariya R, Kudo E, Katano H, Okada S.
|
| タイトル |
PAX5 functions as a tumor suppressor by RB-E2F-mediated cell cycle arrest in Kaposi sarcoma-associated herpesvirus-infected primary effusion lymphoma.
|
| ジャーナル |
Neoplasia
|
| Abstract |
Primary effusion lymphoma (PEL) is a malignant B-cell lymphoma attributable to Kaposi sarcoma-associated herpesvirus (KSHV) infection. PEL is characterized by invasive behavior, showing recurrent effusions in body cavities. The clinical outcome and typical prognosis in patients with PEL are poor and potentially lethal. Clarification of the pathogenesis in PEL is urgently needed in order to develop novel therapies. PEL cells generally lack B-cell surface markers, and we therefore hypothesized that the B-cell transcription factor, PAX5, would be down-regulated in PEL. The expression of PAX5 is detected from the pro-B to the mature B-cell stage and is indispensable for the differentiation of B-cells. PAX5 was silenced in PEL cells via its promoter methylation. Up-regulation of PAX5 induced several genes coding for B-cell surface marker mRNA, but not protein level. PAX5 inhibited cell growth via G1 cell cycle arrest. PAX5 bound to RB and increased its protein expression. RB/E2F-regulated genes were significantly down-regulated in microarray analysis and PCR experiments. To elucidate the in vivo role of PAX5, we examined the restoration of PAX5 in a PEL mouse model. The ascites volume and organ invasions were significantly suppressed by PAX5 restoration. Reduction of PAX5 has played a crucial role in the oncogenesis of PEL, and PAX5 is a tumor suppressor in PEL. Targeting PAX5 could represent a novel therapeutic strategy for patients with PEL.
|
| 巻・号 |
56
|
| ページ |
101035
|
| 公開日 |
2024-10-1
|
| DOI |
10.1016/j.neo.2024.101035
|
| PII |
S1476-5586(24)00077-0
|
| PMID |
39096792
|
| PMC |
PMC11342765
|
| MeSH |
Animals
Cell Cycle Checkpoints* / genetics
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Herpesviridae Infections / complications
Herpesviridae Infections / genetics
Herpesviridae Infections / metabolism
Herpesviridae Infections / virology
Herpesvirus 8, Human* / genetics
Humans
Lymphoma, Primary Effusion* / etiology
Lymphoma, Primary Effusion* / genetics
Lymphoma, Primary Effusion* / metabolism
Lymphoma, Primary Effusion* / pathology
Lymphoma, Primary Effusion* / virology
Mice
PAX5 Transcription Factor* / genetics
PAX5 Transcription Factor* / metabolism
Promoter Regions, Genetic
|
| IF |
5.696
|
| リソース情報 |
| ヒト・動物細胞 |
Raji |
