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Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics
Published on: January 11, 2019
DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis
Yoshizumi Asano1, Satoshi Kishida, Ping Mu
1Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Abstract:
Down-regulated in renal cell carcinoma 1 (DRR1) is mapped at 3p21.1, and is a candidate tumor suppressor gene. However, its biological roles have yet to be elucidated. Here, we developed polyclonal antibodies against DRR1 protein, and examined its expression during embryogenesis and carcinogenesis. The DRR1 protein was preferentially expressed in axonal projections of the central and peripheral nervous system of mice during embryonic days 10.5-16.5. Consistent with this expression pattern, the protein was detected in the neurites of primary cultured cortical neurons of rats at embryonic day 18.5. Survival of these cells was significantly inhibited by RNAi-induced downregulation of DRR1 expression. DRR1 was poorly expressed in established cancer cell lines, including neuroblastoma cells, whereas strong expression was observed in normal cells. A neuroblastoma model, MYCN transgenic mice, revealed that DRR1 protein was expressed in the celiac ganglion 2 weeks after birth when neuroblast hyperplasia was also observed; however, there was no longer any expression of DRR1 protein in tumors originating from the ganglion 8 weeks after birth. Together, our data indicate that DRR1 protein is expressed in normal cells, particularly in the nervous system during embryogenesis, is involved in neuronal cell survival, and is downregulated during neuroblastoma carcinogenesis.
Insights
Down-regulated in renal cell carcinoma 1 (DRR1) protein is crucial for nervous system development and neuronal survival. Its expression is lost during neuroblastoma, suggesting a tumor suppressor role in this cancer.
Area of Science:
- Neuroscience
- Developmental Biology
- Oncology
Background:
- Down-regulated in renal cell carcinoma 1 (DRR1) is a candidate tumor suppressor gene located at 3p21.1.
- The biological functions of DRR1 remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression patterns and biological roles of DRR1 during embryogenesis and carcinogenesis.
- To elucidate the involvement of DRR1 in neuronal cell survival and its potential role in neuroblastoma development.
Main Methods:
- Development of polyclonal antibodies against DRR1 protein.
- Examination of DRR1 expression in mouse embryos (E10.5-16.5) and primary rat cortical neurons.
- RNA interference (RNAi) to downregulate DRR1 expression and assess its impact on neuronal survival.
- Analysis of DRR1 expression in neuroblastoma cell lines and a MYCN transgenic mouse model.
Main Results:
- DRR1 protein exhibited preferential expression in the central and peripheral nervous system axonal projections during mouse embryogenesis.
- DRR1 was detected in neurites of cultured cortical neurons, and its downregulation significantly impaired cell survival.
- DRR1 expression was low in cancer cell lines, including neuroblastoma, but high in normal cells.
- In a neuroblastoma model, DRR1 was initially expressed in hyperplastic ganglia but lost in tumors that developed later.
Conclusions:
- DRR1 protein is expressed in normal cells, particularly within the developing nervous system.
- DRR1 plays a role in neuronal cell survival.
- DRR1 downregulation is associated with neuroblastoma carcinogenesis, supporting its function as a tumor suppressor.
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