Involvement of RQCD1 overexpression, a novel cancer-testis antigen, in the Akt pathway in breast cancer cells.
We here report identification and characterization of required for cell differentiation 1 homolog (RQCD1) as a potential therapeutic target for breast cancer. Gene-expression profiling analysis of breast cancer cells, semi-quantitative RT-PCR, Northern blotting and Western blotting confirmed RQCD1 to be frequently up-regulated in breast cancer specimens and breast cancer cell lines. On the other hand, its expression was very weak or hardly detectable in normal human tissues except testis, indicating this molecule to be a novel cancer-testis antigen. Treatment of breast cancer cell lines with siRNA targeting RQCD1 drastically suppressed cell proliferation. Concordantly, introduction of exogenous RQCD1 into HEK293 cells significantly enhanced cell growth, implying RQCD1 to have an oncogenic activity. Co-immunoprecipitation experiments and immunocytochemical staining revealed an interaction of RQCD1 protein with Grb10 interacting GYF protein 1 (GIGYF1) and 2 (GIGYF2) proteins, involved in regulation of Akt activation, in breast cancer cells. Interestingly, knockdown of either of RQCD1, GIGYF1 or GIGYF2 resulted in significant reduction of the phosphorylation of Akt at Ser 473 in breast cancer cell lines. Our findings suggest that RQCD1 is a potential molecular target for treatment of breast cancer.
Ajiro
Masahiko
M
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Katagiri
Toyomasa
T
Ueda
Koji
K
Nakagawa
Hidewaki
H
Fukukawa
Chikako
C
Lin
Meng-Lay
ML
Park
Jae-Hyun
JH
Nishidate
Toshihiko
T
Daigo
Yataro
Y
Nakamura
Yusuke
Y
D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine; D015398:Signal Transduction; D013737:Testis / Q000276:immunology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
C468527:CNOT9 protein, human; D002352:Carrier Proteins; C478015:GIGYF1 protein, human; C478016:GIGYF2 protein, human; D014157:Transcription Factors; D012694:Serine; D051057:Proto-Oncogene Proteins c-akt