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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder carcinogenesis
M Kanehira1, Y Harada, R Takata
1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Abstract:
In an attempt to disclose mechanisms of bladder carcinogenesis and discover novel target molecules for development of treatment, we applied a cDNA microarray to screen genes that were significantly transactivated in bladder cancer cells. Among the upregulated genes, we here focused on a novel gene, (DEPDC1) DEP domain containing 1, whose overexpression was confirmed by northern blot and immunohistochemical analyses. Immunocytochemical staining analysis detected strong staining of endogenous DEPDC1 protein in the nucleus of bladder cancer cells. Since DEPDC1 expression was hardly detectable in any of 24 normal human tissues we examined except the testis, we considered this gene-product to be a novel cancer/testis antigen. Suppression of DEPDC1 expression with small-interfering RNA significantly inhibited growth of bladder cancer cells. Taken together, these findings suggest that DEPDC1 might play an essential role in the growth of bladder cancer cells, and would be a promising molecular-target for novel therapeutic drugs or cancer peptide-vaccine to bladder cancers.
Insights
Researchers identified DEP domain containing 1 (DEPDC1) as a novel cancer antigen overexpressed in bladder cancer. Suppressing DEPDC1 inhibited cancer cell growth, suggesting it as a promising target for new bladder cancer treatments and vaccines.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Bladder cancer development involves complex genetic alterations.
- Identifying novel molecular targets is crucial for effective bladder cancer treatment.
Purpose of the Study:
- To uncover mechanisms of bladder carcinogenesis.
- To identify novel molecular targets for bladder cancer therapy.
- To investigate the role of DEP domain containing 1 (DEPDC1) in bladder cancer.
Main Methods:
- cDNA microarray screening to identify upregulated genes in bladder cancer cells.
- Northern blot and immunohistochemical analyses to confirm DEPDC1 overexpression.
- Immunocytochemical staining to localize DEPDC1 protein.
- Small-interfering RNA (siRNA) to suppress DEPDC1 expression.
Main Results:
- DEP domain containing 1 (DEPDC1) was significantly upregulated in bladder cancer cells.
- DEPDC1 protein was predominantly localized in the nucleus of bladder cancer cells.
- DEPDC1 expression was detected in normal tissues only in the testis, classifying it as a cancer/testis antigen.
- Suppression of DEPDC1 using siRNA significantly inhibited bladder cancer cell growth.
Conclusions:
- DEP domain containing 1 (DEPDC1) plays a critical role in bladder cancer cell proliferation.
- DEPDC1 is a promising molecular target for novel therapeutic strategies, including drugs and cancer peptide vaccines for bladder cancer.
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