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Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer
Mitsugu Kanehira1, Toyomasa Katagiri, Arata Shimo
1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Abstract:
To disclose the molecular mechanism of bladder cancer, the second most common genitourinary tumor, we had previously done genome-wide expression profile analysis of 26 bladder cancers by means of cDNA microarray representing 27,648 genes. Among genes that were significantly up-regulated in the majority of bladder cancers, we here report identification of M-phase phosphoprotein 1 (MPHOSPH1) as a candidate molecule for drug development for bladder cancer. Northern blot analyses using mRNAs of normal human organs and cancer cell lines indicated this molecule to be a novel cancer-testis antigen. Introduction of MPHOSPH1 into NIH3T3 cells significantly enhanced cell growth at in vitro and in vivo conditions. We subsequently found an interaction between MPHOSPH1 and protein regulator of cytokinesis 1 (PRC1), which was also up-regulated in bladder cancer cells. Immunocytochemical analysis revealed colocalization of endogenous MPHOSPH1 and PRC1 proteins in bladder cancer cells. Interestingly, knockdown of either MPHOSPH1 or PRC1 expression with specific small interfering RNAs caused a significant increase of multinuclear cells and subsequent cell death of bladder cancer cells. Our results imply that the MPHOSPH1/PRC1 complex is likely to play a crucial role in bladder carcinogenesis and that inhibition of the MPHOSPH1/PRC1 expression or their interaction should be novel therapeutic targets for bladder cancers.
Insights
M-phase phosphoprotein 1 (MPHOSPH1) and protein regulator of cytokinesis 1 (PRC1) are crucial in bladder cancer. Inhibiting MPHOSPH1/PRC1 offers a novel therapeutic target for bladder cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer is a prevalent genitourinary malignancy.
- Understanding its molecular mechanisms is key for effective drug development.
- Genome-wide expression profiling is a powerful tool for identifying cancer-related genes.
Purpose of the Study:
- To identify novel molecular targets for bladder cancer therapy.
- To elucidate the role of M-phase phosphoprotein 1 (MPHOSPH1) in bladder cancer.
- To investigate the interaction between MPHOSPH1 and protein regulator of cytokinesis 1 (PRC1).
Main Methods:
- Genome-wide expression profile analysis using cDNA microarray.
- Northern blot analysis to assess MPHOSPH1 expression in normal and cancer tissues.
- In vitro and in vivo cell growth assays after MPHOSPH1 introduction.
- Immunocytochemical analysis to determine MPHOSPH1 and PRC1 colocalization.
- Small interfering RNA (siRNA) knockdown to evaluate the functional impact of MPHOSPH1 and PRC1.
Main Results:
- MPHOSPH1 was identified as a significantly up-regulated gene in bladder cancer and a novel cancer-testis antigen.
- MPHOSPH1 enhanced cell growth in vitro and in vivo.
- MPHOSPH1 interacts with PRC1, another up-regulated protein in bladder cancer cells.
- Knockdown of MPHOSPH1 or PRC1 led to increased multinuclear cells and cell death.
Conclusions:
- The MPHOSPH1/PRC1 complex plays a critical role in bladder carcinogenesis.
- Targeting the MPHOSPH1/PRC1 complex or their interaction presents a promising therapeutic strategy for bladder cancer.
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