Involvement of RQCD1 overexpression, a novel cancer-testis antigen, in the Akt pathway in breast cancer cells

被引:36
作者
Ajiro, Masahiko
Katagiri, Toyomasa [2 ]
Ueda, Koji [3 ]
Nakagawa, Hidewaki [3 ]
Fukukawa, Chikako
Lin, Meng-Lay
Park, Jae-Hyun
Nishidate, Toshihiko
Daigo, Yataro
Nakamura, Yusuke [1 ]
机构
[1] Univ Tokyo, Mol Med Lab, Ctr Human Genome, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan
[2] Univ Tokushima, Div Genome Med, Inst Genome Res, Tokushima 770, Japan
[3] RIKEN, Lab Biomarker Dev, Ctr Genom Med, Yokohama, Kanagawa, Japan
关键词
breast cancer; molecular target; Akt-signal; PROTEIN-KINASE; GENE-EXPRESSION; ELEVATED EXPRESSION; CARCINOGENESIS; ACTIVATION; REGULATOR; MECHANISM; GROWTH; MEMBER;
D O I
10.3892/ijo_00000379
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We here report identification and characterization of Required for Cell Differentiation I 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 I (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.
引用
收藏
页码:673 / 681
页数:9
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