Abstract
Differential display was used to identify genes differentially expressed between cultured normal nasal epithelial cells and nasopharyngeal carcinoma (NPC) cell lines. A 130 bp cDNA fragment showing homology with thyroid hormone receptor α2 (TR-α2 or c-erb A-α2) was identified in NPC cell lines. Northern blot analysis using the 130 bp cDNA fragment and a TR-α2 specific cDNA containing part of the coding region as probes, we were able to detect a 2.7 kb transcript corresponding to that of TR-α2 in NPC cell lines but not in normal nasal epithelial cells. RNA in situ hybridization was used to detect TR-α2 expression in clinical biopsies obtained from NPC patients and non-tumour controls. TR-α2 mRNA was detected in 1 out of 24 (4.2%) normal nasopharynx epithelium biopsies, in 5 out of 27 (18.5%) primary and 15 out of 24 (62.5%) recurrent tumours. The positive rate of TR-α2 expression in recurrent NPC biopsies was significantly higher than that in normal nasopharynx epithelium (P < 0.00001). The relevance of the elevated expression of TR-α2 in the pathogenesis process of NPC was discussed. © 2000 Cancer Research Campaign http://www.bjcancer.com
Keywords: nasopharyngeal carcinoma, c-erb A-α2 (TR-α2), differential display, RNA in situ hybridization
Full Text
The Full Text of this article is available as a PDF (492.9 KB).
Footnotes
Supported in part by National Science Council (NSC 87-2314-B-002-268, NSC 88-2314-B-002-153) and the National Health Research Institute (DOH83-H-315, DOH84-H-315, DOH85-H-315)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barlow C., Meister B., Lardelli M., Lendahl U., Vennström B. Thyroid abnormalities and hepatocellular carcinoma in mice transgenic for v-erbA. EMBO J. 1994 Sep 15;13(18):4241–4250. doi: 10.1002/j.1460-2075.1994.tb06744.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen Y. J., Ko J. Y., Chen P. J., Shu C. H., Hsu M. T., Tsai S. F., Lin C. H. Chromosomal aberrations in nasopharyngeal carcinoma analyzed by comparative genomic hybridization. Genes Chromosomes Cancer. 1999 Jun;25(2):169–175. [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Claudio P. P., Howard C. M., Fu Y., Cinti C., Califano L., Micheli P., Mercer E. W., Caputi M., Giordano A. Mutations in the retinoblastoma-related gene RB2/p130 in primary nasopharyngeal carcinoma. Cancer Res. 2000 Jan 1;60(1):8–12. [PubMed] [Google Scholar]
- Damm K. ErbA: tumor suppressor turned oncogene? FASEB J. 1993 Jul;7(10):904–909. doi: 10.1096/fasebj.7.10.8102105. [DOI] [PubMed] [Google Scholar]
- Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
- Fung L. F., Yuen P. W., Wei W., Kwan H. S., Tsao S. W. Identification of genes differentially expressed in nasopharyngeal carcinoma by messenger RNA differential display. Int J Oncol. 1998 Jul;13(1):85–89. doi: 10.3892/ijo.13.1.85. [DOI] [PubMed] [Google Scholar]
- Glaser R., Zhang H. Y., Yao K. T., Zhu H. C., Wang F. X., Li G. Y., Wen D. S., Li Y. P. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9524–9528. doi: 10.1073/pnas.86.23.9524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hildesheim A., Levine P. H. Etiology of nasopharyngeal carcinoma: a review. Epidemiol Rev. 1993;15(2):466–485. doi: 10.1093/oxfordjournals.epirev.a036130. [DOI] [PubMed] [Google Scholar]
- Hu L. F., Eiriksdottir G., Lebedeva T., Kholodniouk I., Alimov A., Chen F., Luo Y., Zabarovsky E. R., Ingvarsson S., Klein G. Loss of heterozygosity on chromosome arm 3p in nasopharyngeal carcinoma. Genes Chromosomes Cancer. 1996 Oct;17(2):118–126. doi: 10.1002/(SICI)1098-2264(199610)17:2<118::AID-GCC7>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
- Huang D. P., Ho J. H., Chan W. K., Lau W. H., Lui M. Cytogenetics of undifferentiated nasopharyngeal carcinoma xenografts from southern Chinese. Int J Cancer. 1989 May 15;43(5):936–939. doi: 10.1002/ijc.2910430535. [DOI] [PubMed] [Google Scholar]
- Huang D. P., Lo K. W., Choi P. H., Ng A. Y., Tsao S. Y., Yiu G. K., Lee J. C. Loss of heterozygosity on the short arm of chromosome 3 in nasopharyngeal carcinoma. Cancer Genet Cytogenet. 1991 Jul 1;54(1):91–99. doi: 10.1016/0165-4608(91)90035-s. [DOI] [PubMed] [Google Scholar]
- Hui A. B., Lo K. W., Leung S. F., Teo P., Fung M. K., To K. F., Wong N., Choi P. H., Lee J. C., Huang D. P. Detection of recurrent chromosomal gains and losses in primary nasopharyngeal carcinoma by comparative genomic hybridisation. Int J Cancer. 1999 Aug 12;82(4):498–503. doi: 10.1002/(sici)1097-0215(19990812)82:4<498::aid-ijc5>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
- Koenig R. J., Lazar M. A., Hodin R. A., Brent G. A., Larsen P. R., Chin W. W., Moore D. D. Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing. Nature. 1989 Feb 16;337(6208):659–661. doi: 10.1038/337659a0. [DOI] [PubMed] [Google Scholar]
- Lazar M. A., Hodin R. A., Chin W. W. Human carboxyl-terminal variant of alpha-type c-erbA inhibits trans-activation by thyroid hormone receptors without binding thyroid hormone. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7771–7774. doi: 10.1073/pnas.86.20.7771. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lazar M. A., Hodin R. A., Darling D. S., Chin W. W. Identification of a rat c-erbA alpha-related protein which binds deoxyribonucleic acid but does not bind thyroid hormone. Mol Endocrinol. 1988 Oct;2(10):893–901. doi: 10.1210/mend-2-10-893. [DOI] [PubMed] [Google Scholar]
- Lin C. T., Chan W. Y., Chen W., Huang H. M., Wu H. C., Hsu M. M., Chuang S. M., Wang C. C. Characterization of seven newly established nasopharyngeal carcinoma cell lines. Lab Invest. 1993 Jun;68(6):716–727. [PubMed] [Google Scholar]
- Lin C. T., Wong C. I., Chan W. Y., Tzung K. W., Ho J. K., Hsu M. M., Chuang S. M. Establishment and characterization of two nasopharyngeal carcinoma cell lines. Lab Invest. 1990 Jun;62(6):713–724. [PubMed] [Google Scholar]
- Lin K. H., Shieh H. Y., Chen S. L., Hsu H. C. Expression of mutant thyroid hormone nuclear receptors in human hepatocellular carcinoma cells. Mol Carcinog. 1999 Sep;26(1):53–61. doi: 10.1002/(sici)1098-2744(199909)26:1<53::aid-mc7>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- Lu Q. L., Elia G., Lucas S., Thomas J. A. Bcl-2 proto-oncogene expression in Epstein-Barr-virus-associated nasopharyngeal carcinoma. Int J Cancer. 1993 Jan 2;53(1):29–35. doi: 10.1002/ijc.2910530107. [DOI] [PubMed] [Google Scholar]
- Mitelman F., Mark-Vendel E., Mineur A., Giovanella B., Klein G. A 3q+ marker chromosome in EBV-carrying nasopharyngeal carcinomas. Int J Cancer. 1983 Dec 15;32(6):651–655. doi: 10.1002/ijc.2910320602. [DOI] [PubMed] [Google Scholar]
- Mitsuhashi T., Tennyson G. E., Nikodem V. M. Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5804–5808. doi: 10.1073/pnas.85.16.5804. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mutirangura A., Tanunyutthawongese C., Pornthanakasem W., Kerekhanjanarong V., Sriuranpong V., Yenrudi S., Supiyaphun P., Voravud N. Genomic alterations in nasopharyngeal carcinoma: loss of heterozygosity and Epstein-Barr virus infection. Br J Cancer. 1997;76(6):770–776. doi: 10.1038/bjc.1997.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakai A., Seino S., Sakurai A., Szilak I., Bell G. I., DeGroot L. J. Characterization of a thyroid hormone receptor expressed in human kidney and other tissues. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2781–2785. doi: 10.1073/pnas.85.8.2781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porter M. J., Field J. K., Leung S. F., Lo D., Lee J. C., Spandidos D. A., van Hasselt C. A. The detection of the c-myc and ras oncogenes in nasopharyngeal carcinoma by immunohistochemistry. Acta Otolaryngol. 1994 Jan;114(1):105–109. doi: 10.3109/00016489409126025. [DOI] [PubMed] [Google Scholar]
- Spruck C. H., 3rd, Tsai Y. C., Huang D. P., Yang A. S., Rideout W. M., 3rd, Gonzalez-Zulueta M., Choi P., Lo K. W., Yu M. C., Jones P. A. Absence of p53 gene mutations in primary nasopharyngeal carcinomas. Cancer Res. 1992 Sep 1;52(17):4787–4790. [PubMed] [Google Scholar]
- Sun Y., Hegamyer G., Colburn N. H. Nasopharyngeal carcinoma shows no detectable retinoblastoma susceptibility gene alterations. Oncogene. 1993 Mar;8(3):791–795. [PubMed] [Google Scholar]
- Sun Y., Hildesheim A., Lanier A. E., Cao Y., Yao K. T., Raab-Traub N., Yang C. S. No point mutation but decreased expression of the p16/MTS1 tumor suppressor gene in nasopharyngeal carcinomas. Oncogene. 1995 Feb 16;10(4):785–788. [PubMed] [Google Scholar]
- Too C. K., Guernsey D. L. Increased messenger RNA levels of the antagonist thyroid hormone receptor erbA-alpha 2 and decreased levels of erbA-alpha 1 and erbA-beta 1 receptor messenger RNAs in neoplastic rodent cells. Cancer Res. 1992 Apr 15;52(8):2186–2190. [PubMed] [Google Scholar]
- Warrell R. P., Jr, de Thé H., Wang Z. Y., Degos L. Acute promyelocytic leukemia. N Engl J Med. 1993 Jul 15;329(3):177–189. doi: 10.1056/NEJM199307153290307. [DOI] [PubMed] [Google Scholar]
- Zhan F., Jiang N., Cao L., Deng L., Tan G., Zhou M., Xie Y., Li G. [Primary study of differentially expressed cDNA sequences in cell line HNE1 of human nasopharyngeal carcinoma by cDNA representational difference analysis]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1998 Dec 10;15(6):341–344. [PubMed] [Google Scholar]
