Abstract
Astrocytomas are the most common neoplasm of the central nervous system. Although progress has been made, the survival rate of astrocytoma is still poor. Therefore, improving the prognosis of patients with astrocytomas relies on effective therapies that are directed against unique molecular aberrations. Previous studies have revealed that a novel member of the Ras superfamily, RRP22, which is located on chromosome 22 on the 12q site, is exclusively expressed in the central nervous system. RRP22 can be modified by farnesyl and down-regulated in a variety of neural tumor cell lines. In this study, we analyzed the mRNA level of RRP22 in normal brain tissues and astrocytomas using quantitative RT-PCR. Our results showed that the mRNA level in astrocytomas was significantly down-regulated compared to levels in normal tissues. As the pathological grade (World Health Organization (WHO) classification 2007) increased, the expression of RRP22 decreased. However, according to our research, there was no significant difference between malignant astrocytomas with pathological grades of III or IV. To investigate the possible effects of RRP22 on the biological behavior of glioma cells, we transfected RRP22 into a malignant cell line of astrocytomas, U251. We found that RRP22 inhibited growth, decreased invasiveness, and induced cell death. Thus, RRP22 is a special neural tumor suppressor for human astrocytomas, although further studies are needed to define the detailed mechanisms.
Similar content being viewed by others
References
Fuller GN, Scheithauer BW. The 2007 Revised World Health Organization (WHO) classification of tumours of the central nervous system: newly codified entities. Brain Pathol. 2007;17(3):304–7.
Wang L, et al. Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation. J Clin Oncol. 2006;24(10):1627–32.
Lymbouridou R, et al. Down-regulation of K-ras and H-ras in human brain gliomas. Eur J Cancer. 2009;45(7):1294–303.
Guha A, et al. Proliferation of human malignant astrocytomas is dependent on Ras activation. Oncogene. 1997;15(23):2755–65.
Knobbe CB, Reifenberger J, Reifenberger G. Mutation analysis of the Ras pathway genes NRAS, HRAS, KRAS and BRAF in glioblastomas. Acta Neuropathol. 2004;108(6):467–70.
Ligon AH, et al. Identification of a novel gene product, RIG, that is down-regulated in human glioblastoma. Oncogene. 1997;14(9):1075–81.
Yu Y, et al. NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas. Proc Natl Acad Sci U S A. 1999;96(1):214–9.
Zucman-Rossi J, Legoix P, Thomas G. Identification of new members of the Gas2 and Ras families in the 22q12 chromosome region. Genomics 1996 Dec 15 [cited 38 3]; 1996/12/15:247-54.
Elam C, et al. RRP22 is a farnesylated, nucleolar, Ras-related protein with tumor suppressor potential. Cancer Res. 2005;65(8):3117–25.
Prigent SA, et al. Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras-Shc-Grb2 pathway. J Biol Chem. 1996;271(41):25639–45.
Cloughesy TF, et al. Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: a North American brain tumor consortium study. J Clin Oncol. 2006;24(22):3651–6.
Lustig R, et al. Phase II preradiation R115777 (tipifarnib) in newly diagnosed GBM with residual enhancing disease. Neuro Oncol. 2008;10(6):1004–9.
Lu W, et al. Suppression of invasion in human U87 glioma cells by adenovirus-mediated co-transfer of TIMP-2 and PTEN gene. Cancer Lett. 2004;214(2):205–13.
Lakka SS, et al. Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion. Oncogene. 2002;21(52):8011–9.
Van Delft MF, et al. Apoptosis and non-inflammatory phagocytosis can be induced by mitochondrial damage without caspases. Cell Death Differ. 2010;17(5):821–32.
Tait SW, Green DR. Caspase-independent cell death: leaving the set without the final cut. Oncogene. 2008;27(50):6452–61.
Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305(5684):626–9.
Noutsopoulos D, et al. VL30 retrotransposition signals activation of a caspase-independent and p53-dependent death pathway associated with mitochondrial and lysosomal damage. Cell Res. 2010;20(5):553–62.
Xiang J, Chao DT, Korsmeyer SJ. BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases. Proc Natl Acad Sci U S A. 1996;93(25):14559–63.
Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004;6(4):463–77.
Acknowledgments
The work was supported by National Natural Science Foundation of China Grants 30600636 (to Yanjin Wang).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, R., Yang, L., Fang, J. et al. RRP22: a novel neural tumor suppressor for astrocytoma. Med Oncol 29, 332–339 (2012). https://doi.org/10.1007/s12032-010-9795-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-010-9795-6