Abatract
Purpose
To explore the expression of ribosomal protein L7A (RPL7A) in osteosarcoma and its correlation with clinical features.
Methods
Ribosomal protein L7A mRNA expression was quantified by real-time reverse transcription (RT)-polymerase chain reaction (PCR) in 47 specimens from osteosarcoma, 8 from normal bone tissues and 12 from benign bone lesion tissues. Expression of RPL7A mRNA was also detected in human osteosarcoma cell line MG-63. The relationship between RPL7A mRNA expression and clinicopathological factors was statistically analyzed. The immunoblotting pattern of RPL7A was also analyzed in 20 osteosarcomas, 8 normal bone and 8 benign bone tissues.
Results
Ribosomal protein L7A mRNA expression in osteosarcoma samples was significantly down-regulated compared with that in samples from normal bone (P < 0.001) and benign bone lesion tissues (P < 0.001). Low expression of RPL7A mRNA was also found in osteosarcoma cell line MG-63. Low expression of RPL7A mRNA was significantly associated with increased serum level of alkaline phosphatase (ALP, P = 0.008), but was not correlated with other clinicopathological parameters including sex, age, serum lactate dehydrogenase (LDH), tumor location, histological type, histological grading, lung metastasis and overall survival. Interestingly, survival analysis suggested low RPL7A mRNA expression was a significant poor prognostic indicator for overall survival in patients with high grade lesion developed lung metastasis at the time of diagnosis of the primary osteosarcoma (P < 0.05). On western blot, reduced expression of RPL7A protein was observed in osteosarcoma samples (n = 20) compared with normal bone (n = 8) (P < 0.001) and benign bone tissues (n = 8) (P < 0.001).
Conclusion
Under-expression of RPL7A may be involved in the carcinogenesis of osteosarcoma. Loss of RPL7A expression may be associated with poor survival of osteosarcoma patients with lung metastasis.
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References
Amsterdam A, Sadler KC, Lai K et al (2004) Many ribosomal protein genes are cancer genes in zebrafish. PLoS Biol 2(E139):690–698. doi:10.1371/journal.pbio.0020139
Bacci G, Picci P, Ferrari S et al (1993) Prognostic significance of serum alkaline phosphatase measurements in patients with osteosarcoma treated with adjuvant or neoadjuvant chemotherapy. Cancer 71:1224–1230. doi:10.1002/1097-0142(19930215)71:4<1224::AID-CNCR2820710409>3.0.CO;2-M
Bacci G, Longhi A, Ferrari S et al (2004) Prognostic significance of serum lactate dehydrogenase in osteosarcoma of the extremity: experience at Rizzoli on 1,421 patients treated over the last 30 years. Tumori 90:478–484
Bridge JA, Nelson M, McComb E et al (1997) Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature. Cancer Genet Cytogenet 95:74–87. doi:10.1016/S0165-4608(96)00306-8
Burris T, Nawaz Z, Tsal M-J et al (1995) A nuclear hormone receptor-associate protein that inhibits transactivation by the thyroid hormone and retinoic acid receptors. Proc Natl Acad Sci USA 92:9525–9529. doi:10.1073/pnas.92.21.9525
Choesmel V, Fribourg S, Aguissa-Touré AH et al (2008) Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum Mol Genet 17:1253–1263. doi:10.1093/hmg/ddn015
Draptchinskaia N, Gustavsson P, Andersson B et al (1999) The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet 21:169–175. doi:10.1038/5951
Ebert BL, Pretz J, Bosco J et al (2008) Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 451:335–339. doi:10.1038/nature06494
Frodin M, Gammeltoft S (1999) Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol 151:65–77. doi:10.1016/S0303-7207(99)00061-1
Gazda HT, Grabowska A, Merida-Long LB et al (2006) Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet 79:1110–1118. doi:10.1086/510020
Janov AJ, Leong T, Nathan DG et al (1996) Diamond-Blackfan anemia. Natural history and sequelae of treatment. Medicine (Baltimore) 75:77–78. doi:10.1097/00005792-199603000-00004
Kang Y, Shu W, Siegel PM et al (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549. doi:10.1016/S1535-6108(03)00132-6
Kroes RA, Jastrow A, McLone MG et al (2000) The identification of novel therapeutic targets for the treatment of malignant brain tumors. Cancer Lett 156:191–198. doi:10.1016/S0304-3835(00)00462-6
La Quaglia MP (1998) Osteosarcoma Specific tumor management and results. Chest Surg Clin N Am 8:77–95
Lipton JM, Federman N, Khabbaze Y et al (2001) Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry. J Pediatr Hematol Oncol 23:39–44. doi:10.1097/00043426-200101000-00009
Mankin HJ, Gebhardt MC, Jennings LC et al (1996) Long-term results of allograft replacement in the management of bone tumors. Clin Orthop Relat Res 324:86–97. doi:10.1097/00003086-199603000-00011
Martinez MB, Ruan M, Fitzpatrick LA (2000) Altered response to thyroid hormones by prostate and breast cancer cells. Cancer Chemother Pharmacol 45:93–102. doi:10.1007/s002800050016
Miller CW, Aslo A, Tsay C et al (1990) Frequency and structure of p53 rearrangements in human osteosarcoma. Cancer Res 50:7950–7954
Miller CW, Aslo A, Campbell MJ et al (1996) Alterations of the p15, p16, and p18 genes in osteosarcoma. Cancer Genet Cytogenet 86:136–142. doi:10.1016/0165-4608(95)00216-2
Minn AJ, Kang Y, Serganova I et al (2005a) Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest 115:44–55
Minn AJ, Gupta GP, Siegel P et al (2005b) Genes that mediate breast cancer metastasis to lung. Nature 436:518–524. doi:10.1038/nature03799
Noara H (1999) Involvement of ribosomal proteins in regulating cell growth and apoptosis: translational modulation or recruitment for extraribosomal activity? Immunol Cell Biol 77:197–205. doi:10.1046/j.1440-1711.1999.00816.x
Ozaki T, Neumann T, Wai D et al (2003) Chromosomal alterations in osteosarcoma cell lines revealed by comparative genomic hybridization and multicolor karyotyping. Cancer Genet Cytogenet 140:145–152. doi:10.1016/S0165-4608(02)00685-4
Patricia PP, Teixeira SS, Conde SJ et al (2008) The importance of hormone receptor analysis in osteosarcoma cells growth submitted to treatment with estrogen in association with thyroid hormone. Cell Biochem Funct 26:107–110. doi:10.1002/cbf.1408
Sandberg AA, Bridge JA (2003) Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet 145:1–30. doi:10.1016/S0165-4608(03)00105-5
Simsek G, Karter Y, Aydin S et al (2003) Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism. Chin J Physiol 46:181–186
Srivastava A, Fuchs B, Zhang K et al (2006) High WT1 expression is associated with very poor survival of patients with osteogenic sarcoma metastasis. Clin Cancer Res 12:4237–4243. doi:10.1158/1078-0432.CCR-05-2307
Vaarala MH, Porvari KS, Kyllönen AP et al (1998) Several genes encoding ribosomal proteins are over-expressed in prostate-cancer cell lines: confirmation of L7a and L37 over-expression in prostate-cancer tissue samples. Int J Cancer 78:27–32. doi:10.1002/(SICI)1097-0215(19980925)78:1<27::AID-IJC6>3.0.CO;2-Z
van Dijken PJ, Verwijs W (1995) Diamond-Blackfan anemia and malignancy. A case report and a review of the literature. Cancer 76:517–520. doi:10.1002/1097-0142(19950801)76:3<517::AID-CNCR2820760324>3.0.CO;2-8
Wadayama B, Toguchida J, Shimizu T et al (1994) Mutation spectrum of the retinoblastoma gene in osteosarcomas. Cancer Res 54:3042–3048
Wang Y, Cheong D, Chan S et al (2000) Ribosomal protein L7a gene is up-regulated but not fused to the tyrosine kinase receptor as chimeric trk oncogene in human colorectal carcinoma. Int J Oncol 16:757–762
Warner JR, Nierras CR (1998) Trapping human ribosomal protein genes. Genome Res 8:419–421
Wool IG (1996) Extraribosomal functions of ribosomal proteins. Trends Biochem Sci 21:164–165
Yamamoto T (2000) Molecular mechanism of monocyte predominant infiltration in chronic inflammation: mediation by a novel monocyte chemotactic factor, S19 ribosomal protein dimer. Pathol Int 50:863–871. doi:10.1046/j.1440-1827.2000.01132.x
Yamaguchi T, Toguchida J, Yamamuro T et al (1992) Allelotype analysis in osteosarcomas: frequent allele loss on 3q, 13q, 17p, and 18q. Cancer Res 52:2419–2423
Zhu Y, Lin H, Li Z et al (2001) Modulation of expression of ribosomal protein L7a (rpL7a) by ethanol in human breast cancer cells. Breast Cancer Res Treat 69:29–38. doi:10.1023/A:1012293507534
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Zheng, Se., Yao, Y., Dong, Y. et al. Down-regulation of ribosomal protein L7A in human osteosarcoma. J Cancer Res Clin Oncol 135, 1025–1031 (2009). https://doi.org/10.1007/s00432-008-0538-4
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DOI: https://doi.org/10.1007/s00432-008-0538-4