RB1CC1 activates RB1 pathway and inhibits proliferation and cologenic survival in human cancer.
RB1-inducible coiled-coil 1 (RB1CC1, also known as FIP200) plays a role in the enhancement of the RB1 pathway through the direct binding to a GC-rich region 201bp upstream (from the initiation ATG) of the RB1 promoter. Here, we identified hSNF5 and p53 as the binding partners of RB1CC1 by immunoprecipitation and immunofluorescence assays. Interaction between these molecules and the RB1 pathway was analyzed by the assays of chromatin immunoprecipitation, luciferase-reporter, reverse transcription-polymerase chain reaction and immunoblot. The tumor growth suppression by RB1CC1 was evaluated by flow cytometry or by a cell growth assay. The nuclear RB1CC1 complex involving hSNF5 and/or p53 activated transcription of RB1, p16 and p21, and suppressed tumor cell growth. Furthermore, nuclear RB1CC1 expression significantly correlated with those of RB1 and p16 in breast cancer tissue in vivo, and the Ki-67 proliferation index was dependent on p53 as well as RB1CC1. The present study indicates that RB1CC1 together with hSNF5 and/or p53 enhances the RB1 pathway through transcriptional activation of RB1, p16 and p21. Evaluation of RB1CC1 expression combined with RB1 and p53 status is expected to provide useful information in clinical practice and future therapeutic strategies in breast cancer.
Chano
Tokuhiro
T
Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Japan. chano@belle.shiga-med.ac.jp
Ikebuchi
Kaichiro
K
Ochi
Yasuko
Y
Tameno
Hitosuke
H
Tomita
Yasuhiko
Y
Jin
Yufen
Y
Inaji
Hideo
H
Ishitobi
Makoto
M
Teramoto
Koji
K
Nishimura
Ichiro
I
Minami
Kahori
K
Inoue
Hirokazu
H
Isono
Takahiro
T
Saitoh
Masao
M
Shimada
Taketoshi
T
Hisa
Yasuo
Y
Okabe
Hidetoshi
H
D000071183:Autophagy-Related Proteins; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071796:SMARCB1 Protein; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000071183:Autophagy-Related Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C407704:RB1CC1 protein, human; D016160:Retinoblastoma Protein; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases