Abstract
The differentiation-related gene-1 (Drg-1) was first identified as a gene strongly upregulated by induction of differentiation in colon carcinoma cells in vitro, and later the same gene was shown to suppress tumorigenicity of human bladder cancer cells in vivo. On the other hand, we and others have demonstrated that the Drg-1 gene suppresses prostate and colon cancer metastases in mouse models. In the context of such potential organ-specific differential function of the Drg-1 gene, the present study was designed to clarify the expression status, regulation and function of Drg-1 in the case of human breast cancer. We found that the expression of the Drg-1 protein was significantly reduced in breast tumor cells, particularly in patients with lymph node or bone metastasis as compared to those with localized breast cancer. Drg-1 expression also exhibited significant inverse correlation with the disease-free survival rate of patients and emerged as an independent prognostic factor. The downregulation of the Drg-1 gene appeared to be largely at the RNA level, and the DNA methylation inhibitor, 5-Azacytidine, significantly elevated the Drg-1 gene expression in various breast tumor cell lines. Furthermore, we found that overexpression of the Drg-1 gene suppresses the invasiveness of breast cancer cells in vitro, and this suppression was also achieved by treatment of cells with 5-Azacytidine. Together, our results strongly suggest functional involvement of the Drg-1 gene in suppressing the metastatic advancement of human breast cancer.
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References
Bandyopadhyay S, Pai SK, Gross SC, Hirota S, Hosobe S, Miura K, Saito K, Commes T, Hayashi S, Watabe M and Watabe K . (2003). Cancer Res., 63, 1731–1736.
Davol PA, Bagdasaryan R, Elfenbein GJ, Maizel AL and Frackelton Jr AR . (2003). Cancer Res., 6, 6772–6783.
Evron E, Dooley WC, Umbricht CB, Rosenthal D, Sacchi N, Gabrielson E, Soito AB, Hung DT, Jung B, Davidson NE and Sukumar S . (2001). Lancet, 57, 335–336.
Guan RJ, Ford HL, Fu Y, Li Y, Shaw LM and Pardee AB . (2000). Cancer Res., 60, 749–755.
Hartsough MT, Clare SE, Mair M, Elkahloun AG, Sgroi D, Osborne CK, Clark G and Steeg PS . (2001). Cancer Res., 61, 2320–2327.
Kim HL, Vander Griend DJ, Yang X, Benson DA, Dubauskas Z, Yoshida BA, Chekmareva MA, Ichikawa Y, Sokoloff MH, Zhan P, Karrison T, Lin A, Stadler WM, Ichikawa T, Rubin MA and Rinker-Schaeffer CW . (2001). Cancer Res., 61, 2833–2837.
Kokame K, Kato H and Miyata T . (1996). J. Biol. Chem., 271, 29659–29665.
Krueger JS, Keshamouni VG, Atanaskova N and Reddy KB . (2001). Oncogene, 20, 4209–4218.
Kurdistani SK, Arizti P, Reimer CL, Sugrue MM, Aaronson SA and Lee SW . (1998). Cancer Res., 58, 4439–4444.
Lin TM and Chang C . (1997). Proc. Natl. Acad. Sci. USA, 94, 4988–4993.
Masuda K, Ono M, Okamoto M, Morikawa W, Otsubo M, Migita T, Tsuneyoshi M, Okuda H, Shuin T, Naito S and Kuwano M . (2003). Int. J. Cancer., 105, 803–810.
Okuda T and Kondoh H . (1999). Biochem. Biophys. Res. Commun., 266, 208–215.
Park H, Adams MA, Lachat P, Bosman F, Pang SC and Graham CH . (2000). Biochem. Biophys. Res. Commun., 276, 321–328.
Ulrix W, Swinnen JV, Heyns W and Verhoeven G . (1999). FEBS Lett., 455, 23–26.
Unoki M and Nakamura Y . (2001). Oncogene, 20, 4457–4465.
van Belzen N, Dinjens WN, Diesveld MP, Groen NA., van der Made AC, Nozawa Y, Vlietstra R, Trapman J and Bosman FT . (1997). Lab. Invest., 77, 85–92.
Yamada SD, Hickson JA, Hrobowski Y, Vander Griend DJ, Benson D, Montag A, Karrison T, Huo D, Rutgers J, Adams S and Rinker-Schaeffer CW . (2002). Cancer Res., 62, 6717–6723.
Zhou D, Salnikow K and Costa M . (1998). Cancer Res., 58, 2182–2189.
Acknowledgements
This work was supported by NIH (1R15V50079473, 5R01CA89438), DOD (PC031038), Illinois Department of Public Health, and American Lung Association, Illinois.
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Bandyopadhyay, S., Pai, S., Hirota, S. et al. Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression. Oncogene 23, 5675–5681 (2004). https://doi.org/10.1038/sj.onc.1207734
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DOI: https://doi.org/10.1038/sj.onc.1207734
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