RB1CC1 activates the promoter and expression of RB1 in human cancer

RB1‐inducible coiled‐coil 1 (RB1CC1, also known as FIP200) is a tumor suppressor implicated in the regulation of RB1 (retinoblastoma 1) expression. However, the molecular mechanism of RB1 regulation by RB1CC1 has not been elucidated. Here, we demonstrate that nuclear RB1CC1 binds to the RB1 promoter...

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Bibliographic Details
Published in:International journal of cancer 2009-08, Vol.125 (4), p.861-867
Main Authors: Ikebuchi, Kaichiro, Chano, Tokuhiro, Ochi, Yasuko, Tameno, Hitosuke, Shimada, Taketoshi, Hisa, Yasuo, Okabe, Hidetoshi
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blotting, Western
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell Nucleus - metabolism
Chromatin Immunoprecipitation
Cytoplasm - metabolism
Electrophoretic Mobility Shift Assay
Female
GC Rich Sequence
Gene Expression Regulation, Neoplastic
Humans
Immunoenzyme Techniques
Luciferases - metabolism
Medical sciences
promoter
Promoter Regions, Genetic - genetics
Protein-Tyrosine Kinases - metabolism
RB1
RB1CC1
Retinoblastoma Protein - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
transcription
Transfection
Tumor Cells, Cultured
Tumors
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Summary:RB1‐inducible coiled‐coil 1 (RB1CC1, also known as FIP200) is a tumor suppressor implicated in the regulation of RB1 (retinoblastoma 1) expression. However, the molecular mechanism of RB1 regulation by RB1CC1 has not been elucidated. Here, we demonstrate that nuclear RB1CC1 binds to the RB1 promoter using chromatin immunoprecipitation assays with anti‐RB1CC1 antibody. Luciferase assays with RB1 promoter reporter plasmids revealed that RB1CC1 activated the RB1 promoter through the 201 bp upstream GC‐rich region (from the initiation ATG). Electrophoretic mobility shift assay and Western blot analysis supported RB1CC1 binding to the GC‐rich region of the RB1 promoter. In addition, the C‐terminus of RB1CC1 was required for nuclear localization and subsequent RB1 promoter activation. Furthermore, the expression levels of RB1CC1 and RB1 significantly correlated with in vivo breast cancer tissues as determined by immunohistochemical analysis. These data indicate that nuclear RB1CC1 directly activates the RB1 promoter to enhance RB1 expression in cancer cells. Evaluation of RB1CC1 in various types of human cancer tissues is expected to provide useful information for clinical practice and future therapeutic strategies. © 2009 UICC
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.24466