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Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1.

Publication ,  Journal Article
Chien, W-M; Rabin, S; Macias, E; Miliani de Marval, PL; Garrison, K; Orthel, J; Rodriguez-Puebla, M; Fero, ML
Published in: Proc Natl Acad Sci U S A
March 14, 2006

Loss of the cyclin-dependent kinase inhibitor p27(Kip1) leads to an overall increase in animal growth, pituitary tumors, and hyperplasia of hematopoietic organs, yet it is unknown whether all cells function autonomously in response to p27(Kip1) activity or whether certain cells take cues from their neighbors. In addition, there is currently no genetic evidence that tumor suppression by p27(Kip1) is cell-autonomous because biallelic gene inactivation is absent from tumors arising in p27(Kip1) hemizygous mice. We have addressed these questions with tissue-specific targeted mouse mutants and radiation chimeras. Our results indicate that the suppression of pars intermedia pituitary tumors by p27(Kip1) is cell-autonomous and does not contribute to overgrowth or infertility phenotypes. In contrast, suppression of spleen growth and hematopoietic progenitor expansion is a consequence of p27(Kip1) function external to the hematopoietic compartment. Likewise, p27(Kip1) suppresses thymocyte hyperplasia through a cell-nonautonomous mechanism. The interaction of p27(Kip1) loss with epithelial cell-specific cyclin-dependent kinase 4 overexpression identifies the thymic epithelium as a relevant site of p27(Kip1) activity for the regulation of thymus growth.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 14, 2006

Volume

103

Issue

11

Start / End Page

4122 / 4127

Location

United States

Related Subject Headings

  • Thymus Gland
  • Spleen
  • Radiation Chimera
  • Pituitary Neoplasms
  • Pituitary Gland
  • Mutation
  • Mosaicism
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chien, W.-M., Rabin, S., Macias, E., Miliani de Marval, P. L., Garrison, K., Orthel, J., … Fero, M. L. (2006). Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1. Proc Natl Acad Sci U S A, 103(11), 4122–4127. https://doi.org/10.1073/pnas.0509514103
Chien, Wei-Ming, Stuart Rabin, Everardo Macias, Paula L. Miliani de Marval, Kendra Garrison, Jason Orthel, Marcelo Rodriguez-Puebla, and Matthew L. Fero. “Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1.Proc Natl Acad Sci U S A 103, no. 11 (March 14, 2006): 4122–27. https://doi.org/10.1073/pnas.0509514103.
Chien W-M, Rabin S, Macias E, Miliani de Marval PL, Garrison K, Orthel J, et al. Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4122–7.
Chien, Wei-Ming, et al. “Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1.Proc Natl Acad Sci U S A, vol. 103, no. 11, Mar. 2006, pp. 4122–27. Pubmed, doi:10.1073/pnas.0509514103.
Chien W-M, Rabin S, Macias E, Miliani de Marval PL, Garrison K, Orthel J, Rodriguez-Puebla M, Fero ML. Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4122–4127.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 14, 2006

Volume

103

Issue

11

Start / End Page

4122 / 4127

Location

United States

Related Subject Headings

  • Thymus Gland
  • Spleen
  • Radiation Chimera
  • Pituitary Neoplasms
  • Pituitary Gland
  • Mutation
  • Mosaicism
  • Mice, Transgenic
  • Mice, Knockout
  • Mice