The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Subtle variations in Pten dose determine cancer susceptibility
Open accessAbstract
Cancer susceptibility has been attributed to at least one heterozygous genetic alteration in a tumor suppressor gene (TSG). It has been hypothesized that subtle variations in TSG expression can promote cancer development. However, this hypothesis has not yet been definitively supported in vivo. Pten is a TSG frequently lost in human cancer and mutated in inherited cancer-predisposition syndromes. Here we analyze Pten hypermorphic mice (Ptenhy/+), expressing 80% normal levels of Pten. Ptenhy/+ mice develop a spectrum of tumors, with breast tumors occurring at the highest penetrance. All breast tumors analyzed here retained two intact copies of Pten and maintained Pten levels above heterozygosity. Notably, subtle downregulation of Pten altered the steady-state biology of the mammary tissues and the expression profiles of genes involved in cancer cell proliferation. We present an alterative working model for cancer development in which subtle reductions in the dose of TSGs predispose to tumorigenesis in a tissue-specific manner.
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Cites
Pten is essential for embryonic development and tumour suppression
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Self-citationThe Multiple Roles of PTEN in Tumor Suppression
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Self-citationTwo genetic hits (more or less) to cancer
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Tenets of PTEN Tumor Suppression
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Self-citationMutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems
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Pten Dose Dictates Cancer Progression in the Prostate
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Cited by
The functions and regulation of the PTEN tumour suppressor
Song, M. S., Salmena, L., & Pandolfi, P. P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3330 · Cited by 1,926
Self-citationPhosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270
Self-citationCoding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous mRNAs
Tay, Y., Kats, L., Salmena, L., Weiss, D., Tan, S. M., Ala, U., Karreth, F., Poliseno, L., Provero, P., Di Cunto, F., et al. (2011) · Cell · doi:10.1016/j.cell.2011.09.029 · Cited by 1,019
Self-citationThe functions and regulation of the PTEN tumour suppressor: new modes and prospects
Lee, Y.-R., Chen, M., & Pandolfi, P. P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0015-0 · Cited by 917
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Metadata
- Authors
- Alimonti, A., Carracedo, A., Clohessy, J. G., Trotman, L. C., Nardella, C., Egia, A., Salmena, L., Sampieri, K., Haveman, W. J., Brogi, E., Richardson, A. L., Zhang, J., & Pandolfi, P. P.
- Venue
- Nature Genetics
- Published
- 2010-04-18
- Volume
- 42
- Issue
- 5
- Pages
- 454-458
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2126008912
- Cited by
- 580
- References
- 20
- FWCI
- 21.50
- Type
- journal article
- Language
- en
- Open access
- green
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- Alimonti, A., Carracedo, A., Clohessy, J. G., Trotman, L. C., Nardella, C., Egia, A., Salmena, L., Sampieri, K., Haveman, W. J., Brogi, E., Richardson, A. L., Zhang, J., & Pandolfi, P. P. (2010). Subtle variations in Pten dose determine cancer susceptibility. Nature Genetics. https://doi.org/10.1038/ng.556
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