title: Transcriptional regulation of BMCC1 mediated by E2F1 in neuroblastoma cells.
abstract: BCH motif-containing molecule at the carboxyl terminal region 1 (BMCC1)/PRUNE2 is highly expressed in patients with favorable neuroblastoma (NB), encoding a multifunctional scaffold protein that modulates several signaling networks including RhoA and AKT pathways. Accumulating evidence suggests that BMCC1 acts as a tumor-suppressor. In this study, we addressed molecular mechanism underlying transcriptional regulation of BMCC1 in NBs. We found that transcription factor E2F1 was recruited to E2F-binding site in the promoter region of BMCC1 gene. Indeed, overexpression of E2F1 resulted in an increase in the expression level of BMCC1 in NB cell lines. On the other hand, knockdown of E2F1 in NB cells yielded down-regulation of BMCC1. Also, we showed that BMCC1 and E2F1 were simultaneously induced at G1 to S phase transition. Therefore, we conclude that E2F1 directly facilitated BMCC1 transcription. Taking together, these results suggest that BMCC1 induced by E2F1 acts as a tumor suppressor through its pro-apoptotic function, resulted in favorable prognosis of NB.
authors.affiliation: Laboratory of Innovative Cancer Therapeutics, Japan; Department of Molecular Biology and Oncology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Mohammad Sazzadul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Laboratory of Innovative Cancer Therapeutics, Japan; Laboratory of Oncogenomics, Japan. Electronic address: ytatsumi@chiba-cc.jp.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Tatsumi
authors.affiliation: Laboratory of Innovative Cancer Therapeutics, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takano
authors.affiliation: Laboratory of Innovative Cancer Therapeutics, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yokochi
authors.affiliation: Laboratory of Innovative Cancer Therapeutics, Japan.
authors.forename: Jesmin
authors.initials: J
authors.lastname: Akter
authors.affiliation: Laboratory of DNA Damage Signaling, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Laboratory of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Laboratory of Oncogenomics, Japan; Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ohira
authors.affiliation: Saga Medical Center KOSEIKAN, Saga, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009363:Neoplasm Proteins; C509845:PRUNE2 protein, human
keywords: BMCC1/PRUNE2; Cell cycle; E2F1; Neuroblastoma