DOI: 10.1002/ijc.20014. Reduction of TSG101 protein has a negative impact on tumor cell growth

Reduction of TSG101 protein has a negative impact on tumor cell growth

10.1002/ijc.20014

Crossref journal-article

Wiley

International Journal of Cancer (311)

Abstract

AbstractTSG101 was defined originally as a tumor‐suppressor gene, raising the expectation that absence of the encoded protein should lead to increased tumor cell growth and, perhaps, increased tumor cell aggressiveness. We have used the RNA interference (RNAi) technique to downregulate TSG101 in PC3 (prostate cancer) and MDA‐MB‐231 (breast cancer) cells. An approximately 85% selective downregulation at the protein level was achieved in both cell lines over a period of 12 days as detected by Western blotting. This treatment resulted in inhibition of tumor cell growth, with a decreased level of TSG101 causing partial cell cycle arrest at the G1/S boundary and a reduction in the rate at which cells passed from G2 through mitosis and back into G1. In both cell lines, the percentage of cells in S‐phase was reduced significantly at day 4 after the TSG101 siRNA transfection (27% vs. 41% in MDA‐MB‐231 cells; 22% vs. 39% in PC3 cells). Additionally, RNAi‐mediated downregulation of TSG101 reduced the colony formation capacities of both cancer cell lines. Rather more surprisingly, TSG101 downregulation affected the migratory activity of the MDA‐MB‐231 cells, independent of any effect on proliferation. Thus, in a Transwell assay, after 4‐hr incubation, 36.0% of control MDA‐MB‐231 cells had migrated to the lower chamber vs. 7.3% of TSG101‐downregulated cells (p < 0.001; scrambled control, 36.5%). These results show that the TSG101 gene does not comply with the usual characteristics of a tumor‐suppressor gene; rather, its expression may be necessary for activities associated with aspects of tumor progression. © 2004 Wiley‐Liss, Inc.

Bibliography

Zhu, G., Gilchrist, R., Borley, N., Chng, H. W., Morgan, M., Marshall, J. F., Camplejohn, R. S., Muir, G. H., & Hart, I. R. (2004). Reduction of TSG101 protein has a negative impact on tumor cell growth. International Journal of Cancer, 109(4), 541â547. Portico.

Authors 9

Gang Zhu (first)
Ruth Gilchrist (additional)
Nigel Borley (additional)
Hsiao Wee Chng (additional)
Mark Morgan (additional)
John F. Marshall (additional)
Richard S. Camplejohn (additional)
Gordon H. Muir (additional)
Ian R. Hart (additional)

References 22 Referenced 37

10.1038/sj.onc.1206428
10.1038/bjc.1994.287
10.1016/S0092-8674(00)81111-3
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{'key': 'e_1_2_5_6_2', 'first-page': '1736', 'article-title': 'TSG101 protein steady‐state level is regulated posttranslationally by an evolutionarily conserved COOH‐terminal sequence', 'volume': '60', 'author': 'Feng GH', 'year': '2000', 'journal-title': 'Cancer Res'} / Cancer Res / TSG101 protein steady‐state level is regulated posttranslationally by an evolutionarily conserved COOH‐terminal sequence by Feng GH (2000)
{'key': 'e_1_2_5_7_2', 'first-page': '2699', 'article-title': 'Perturbation of TSG101 protein affects cell cycle progression', 'volume': '58', 'author': 'Zhong Q', 'year': '1998', 'journal-title': 'Cancer Res'} / Cancer Res / Perturbation of TSG101 protein affects cell cycle progression by Zhong Q (1998)
10.1074/jbc.M207662200
{'key': 'e_1_2_5_9_2', 'first-page': '387', 'article-title': 'A novel 4‐cM minimally deleted region on chromosome 11p15.1 associated with high grade nonmucinous epithelial ovarian carcinomas', 'volume': '57', 'author': 'Lu KH', 'year': '1997', 'journal-title': 'Cancer Res'} / Cancer Res / A novel 4‐cM minimally deleted region on chromosome 11p15.1 associated with high grade nonmucinous epithelial ovarian carcinomas by Lu KH (1997)
10.1038/ng0897-332
10.1073/pnas.95.4.1595
10.1038/bjc.1998.86
10.1002/cyto.990060618
10.1046/j.1365-2184.1999.3210015.x
10.1016/S0092-8674(00)81866-8
{'key': 'e_1_2_5_16_2', 'first-page': '3131', 'article-title': 'Aberrant splicing but not mutations of TSG101 in human breast cancer', 'volume': '57', 'author': 'Lee MP', 'year': '1997', 'journal-title': 'Cancer Res'} / Cancer Res / Aberrant splicing but not mutations of TSG101 in human breast cancer by Lee MP (1997)
{'key': 'e_1_2_5_17_2', 'first-page': '1187', 'article-title': 'TSG101 expression in gynaecological tumors; relationship to cyclin D1, cyclin E, p53 and p16 proteins', 'volume': '47', 'author': 'Bennett NA', 'year': '2001', 'journal-title': 'Cell Mol Biol'} / Cell Mol Biol / TSG101 expression in gynaecological tumors; relationship to cyclin D1, cyclin E, p53 and p16 proteins by Bennett NA (2001)
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10.1038/sj.onc.1201133

Dates

Type	When
Created	21 years, 6 months ago (Feb. 26, 2004, 3:30 p.m.)
Deposited	1 year, 9 months ago (Nov. 17, 2023, 4:48 p.m.)
Indexed	4 months, 2 weeks ago (April 16, 2025, 11:26 a.m.)
Issued	21 years, 7 months ago (Jan. 22, 2004)
Published	21 years, 7 months ago (Jan. 22, 2004)
Published Online	21 years, 7 months ago (Jan. 22, 2004)
Published Print	21 years, 4 months ago (April 20, 2004)

Funders 0

None

BibTeX

@article{Zhu_2004, title={Reduction of TSG101 protein has a negative impact on tumor cell growth}, volume={109}, ISSN={1097-0215}, url={http://dx.doi.org/10.1002/ijc.20014}, DOI={10.1002/ijc.20014}, number={4}, journal={International Journal of Cancer}, publisher={Wiley}, author={Zhu, Gang and Gilchrist, Ruth and Borley, Nigel and Chng, Hsiao Wee and Morgan, Mark and Marshall, John F. and Camplejohn, Richard S. and Muir, Gordon H. and Hart, Ian R.}, year={2004}, month=jan, pages={541–547} }

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