Abstract
Functional inactivation of tumor susceptibility gene tsg101 leads to cellular transformation and tumorigenesis in mice. While human TSG101 is located in a region where frequent loss of heterozygosity can be detected in a variety of cancers, no genomic deletion in TSG101 gene has been reported, casting a doubt on the role of TSG101 as a classical tumor suppressor. Some studies have revealed that TSG101 is a frequent target of splicing defects, which correlate with cellular stress and p53 status. Furthermore, recent reports have identified TSG101 as a part of the MDM2/p53 regulatory circuitry, a well-recognized circuitry that upon deregulation results in tumorigenesis. Interestingly, overexpression of tsg101 from an adventitious promoter also leads to neoplastic transformation. On the basis of this information, we have analysed TSG101 gene expression in 20 human papillary thyroid carcinomas (PTCs) by immunohistochemistry and demonstrated that the overexpression of TSG101 protein is closely associated with human PTCs. Further sequence analysis reveals no mutation in cDNA region encoding steadiness box in these PTC specimens, indicating that the upregulation of TSG101 protein is not caused by the alteration of this region. In situ hybridization analysis confirms that overexpression of TSG101 also occurs at the transcriptional level. In addition, semi-quantitative RT–PCR and subsequent Southern hybridization verify that the amounts of TSG101 transcripts are indeed lower in three normal thyroid tissues than in PTC specimens. Here we report the upregulation of TSG101 expression in PTC cells, providing the first evidence of the association of TSG101 overexpression with human tumors and suggesting that upregulation of TSG101 steady-state level might play a role in mediating tumorigenesis of human PTC.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Abbreviations
- TSG101:
-
tumor susceptibility gene 101
- PTC:
-
papillary thyroid carcinoma
- IHC:
-
immunohistochemistry
- ISH:
-
in situ hybridization
- GST:
-
glutathione S-transferase
References
Ali IU, Lidereau R, Theillet C, Callahan R . 1987 Science 238: 185–188
Babst M, Odorizzi G, Estepa EJ, Emr SD . 2000 Traffic 1: 248–258
Baffa R, Negrini M, Mandes B, Rugge M, Ranzani GN, Hirohashi S, Croce CM . 1996 Cancer Res. 56: 268–272
Bishop N, Woodman P . 2000 J. Biol. Chem. 276: 11735–11742
Byrne JA, Simms LA, Little MH, Algar EM, Smith PJ . 1993 Genes Chrom. Cancer 8: 104–111
Carney ME, Maxwell GL, Lancaster JM, Gumbs C, Marks J, Berchuck A, Futreal PA . 1998 J. Soc. Gynecol. Investig. 5: 281–285
Chang JG, Su TH, Wei HJ, Wang JC, Chen YJ, Chang CP, Jeng CJ . 1999 Br. J. Cancer 79: 445–450
Feng GH, Lih CJ, Cohen SN . 2000 Cancer Res. 60: 1736–1741
Hittelman AB, Burakov D, Iñiguez-Lluhí JA, Freedman LP, Garabedian MJ . 1999 EMBO J. 18: 5380–5388
Hsu SF, Chang AC, Wang JK, Cheng JT . 1998 Hybridoma 17: 251–255
Jennings T, Bratslavsky G, Gerasimov G, Troshina K, Bronstein M, Dedov I, Alexandrova G, Figge J . 1995 Exp. Mol. Pathol. 62: 199–206
Koonin EV, Abagyan RA . 1997 Nat. Genet. 16: 330–331
Lee MP, Feinberg AP . 1997 Cancer Res. 57: 3131–3134
Li L, Cohen SN . 1996 Cell 85: 319–329
Li L, Li X, Francke U, Cohen SN . 1997 Cell 88: 143–154
Li L, Liao J, Ruland J, Mak TW, Cohen SN . 2001 Proc. Natl. Acad. Sci. USA 98: 1619–1624
Lin PM, Liu TC, Chang JG, Chen TP, Lin SF . 1998a Br. J. Haematol. 102: 753–758
Lin SY, Chen YJ, Chang JG . 1998b J. Gastroenterol. Hepatol. 13: 1111–1114
Lothe RA, Hastie N, Heimdal K, Fossa SD, Stenwig AE, Borresen AL . 1993 Genes Chrom. Cancer 7: 96–101
Ludwig CU, Raefle G, Dalquen P, Stulz P, Stahel R, Obrecht JP . 1991 Int. J. Cancer 49: 661–665
Maucuer A, Camonis JH, Sobel A . 1995 Proc. Natl. Acad. Sci. USA 92: 3100–3104
McIver B, Grebe SK, Wang L, Hay ID, Yokomizo A, Liu W, Goellner JR, Grant CS, Smith DI, Eberhardt NL . 2000 Clin. Endocrinol. (Oxf) 52: 749–757
Moyret-Lalle C, Duriez C, Van Kerckhove J, Gilbert C, Wang Q, Puisieux A . 2001 Cancer Res. 61: 486–488
Ponting CP, Cai YD, Bork P . 1997 J. Mol. Med. 75: 467–489
Reeve AE, Sih SA, Raizis AM, Feinberg AP . 1989 Mol. Cell. Biol. 9: 1799–1803
Rountree MR, Bachman KE, Baylin SB . 2000 Nat. Genet. 3: 269–277
Ruland J, Sirard C, Elia A, MacPherson D, Wakeham A, Li L, de la Pompa JL, Cohen SN, Mak TW . 2001 Proc. Natl. Acad. Sci. USA 98: 1859–1864
Shaw ME, Knowles MA . 1995 Genes Chrom. Cancer 13: 1–8
Sun Z, Pan J, Hope WX, Cohen SN, Balk SP . 1999 Cancer 86: 689–696
Turpin E, Dalle B, de Roquancourt A, Plassa LF, Marty M, Janin A, Beuzard Y, de The H . 1999 Oncogene 18: 7834–7837
Wang NM, Chang JG, Liu TC, Lin SF, Peng CT, Tsai FJ, Tsai CH . 2000 Int. J. Oncol. 16: 75–80
Watanabe M, Yanagi Y, Masuhiro Y, Yano T, Yoshikawa H, Yanagisawa J, Kato S . 1998 Biochem. Biophys. Res. Commun. 245: 900–905
Weitzel JN, Patel J, Smith DM, Goodman A, Safaii H, Ball HG . 1994 Gynecol. Oncol. 55: 245–252
Willeke F, Ridder R, Bork P, Klaes R, Mechtersheimer G, Schwarzbach M, Zimmer D, Kloor M, Lehnert T, Herfarth C, von Knebel Doeberitz M . 1998 Mol. Carcinog. 23: 195–200
Xie W, Li L, Cohen SN . 1998 Proc. Natl. Acad. Sci. USA 95: 1595–1600
Zhong Q, Chen Y, Jones D, Lee WH . 1998 Cancer Res. 58: 2699–2702
Acknowledgements
We thank Ms Shang-Yun Liu for the assistance in immunohistochemical analysis. This work is supported in part by National Science Council grants NSC 88-2314-B-182A-046 (to R-T Liu), NSC 88-2314-B-110-007 and VGHNSU88-07 (to J-T Cheng).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Liu, RT., Huang, CC., You, HL. et al. Overexpression of tumor susceptibility gene TSG101 in human papillary thyroid carcinomas. Oncogene 21, 4830–4837 (2002). https://doi.org/10.1038/sj.onc.1205612
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205612
Keywords
This article is cited by
-
TSG101 Promotes the Proliferation, Migration, and Invasion of Human Glioma Cells by Regulating the AKT/GSK3β/β-Catenin and RhoC/Cofilin Pathways
Molecular Neurobiology (2021)
-
Knockdown of ANXA10 inhibits proliferation and promotes apoptosis of papillary thyroid carcinoma cells by down-regulating TSG101 thereby inactivating the MAPK/ERK signaling pathway
Journal of Bioenergetics and Biomembranes (2021)
-
siRNA against TSG101 reduces proliferation and induces G0/G1 arrest in renal cell carcinoma – involvement of c-myc, cyclin E1, and CDK2
Cellular & Molecular Biology Letters (2019)
-
Tumor-derived exosomes, myeloid-derived suppressor cells, and tumor microenvironment
Journal of Hematology & Oncology (2019)
-
Extracellular vesicles in onco-nephrology
Experimental & Molecular Medicine (2019)