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Elevated expression of C10orf3 (chromosome 10 open reading frame 3) is involved in the growth of human colon tumor

Abstract

After analysing gene-expression profiles of colon cancers on a cDNA microarray containing cDNAs corresponding to 23 040 human genes, we focused on a gene annotated as C10orf3 (chromosome 10 open reading frame 3), whose expression was elevated in colorectal cancers (CRC) as well as in tumors arising in the stomach, lung, pancreas, and breast. The gene encodes a putative 464-amino-acid protein containing a domain known as AAA (ATPases associated with a variety of cellular activities). Western blot analysis using an antibody to the gene product confirmed that the protein was overexpressed in nine of the 15 clinical cancer tissues examined, compared to corresponding noncancerous epithelial cells. A subsequent proteomics analysis revealed that C10orf3 product associated with the product of tumor susceptibility gene 101 (TSG101), and that C10orf3 downregulated TSG101 in a post-transcriptional manner. Expression of short interfering RNA in cells derived from CRC caused significant decreases in C10orf3 expression and inhibited growth of the transfected cells, which was associated with increased apoptotic cells. These data suggest that elevated C10orf3 expression might play an essential role in the growth of cancer cells, and that suppression of C10orf3-mediated signal transduction may be a novel therapeutic strategy to a wide range of human tumors.

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Acknowledgements

We appreciate the technical assistance of Yoshika Sakamoto, Noriko Ikawa, and Tae Makino and the contributions of Dr Toyomasa Katagiri for the preparation of anti-C10orf3 antibody, and are grateful to Ryuji Hamamoto and Kazutaka Obama for helpful discussions. This work was supported in part by the Research for the Future Program Grant #00L01402 from the Japan Society for the Promotion of Science.

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Correspondence to Y Furukawa.

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Sakai, M., Shimokawa, T., Kobayashi, T. et al. Elevated expression of C10orf3 (chromosome 10 open reading frame 3) is involved in the growth of human colon tumor. Oncogene 25, 480–486 (2006). https://doi.org/10.1038/sj.onc.1209051

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Keywords

  • colon
  • cancer
  • C10orf3
  • TSG101

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