p27 deficiency desensitizes Rb-/- cells to signals that trigger apoptosis during pituitary tumor development

Carmen Carneiro; Maria Socorro Jiao; Ming Hu; David Shaffer; Michele Park; Pier Paolo Pandolfi; Carlos Cordon-Cardo; Andrew Koff

doi:10.1038/sj.onc.1206163

p27 deficiency desensitizes Rb-/- cells to signals that trigger apoptosis during pituitary tumor development

Oncogene. 2003 Jan 23;22(3):361-9. doi: 10.1038/sj.onc.1206163.

Authors

Carmen Carneiro¹, Maria Socorro Jiao, Ming Hu, David Shaffer, Michele Park, Pier Paolo Pandolfi, Carlos Cordon-Cardo, Andrew Koff

Affiliation

¹ Department of Molecular Biology, Menmorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

PMID: 12545157
DOI: 10.1038/sj.onc.1206163

Abstract

Low p27 expression in many human cancers is a prognostic indicator for poor outcome. While analysing the mechanism by which p27 deficiency contributed to tumor development in the Rb+/- mouse model, we identified a role for p27 as a proapoptotic tumor suppressor. We examined the cell cycle and apoptotic response of these pituitary tumor cells to the dopamine analog bromocriptine as well as the expression of Arf and other cell cycle and apoptotic regulators in these tumors. We also examined the expression of Arf and its function in mouse embryo fibroblasts either singly or doubly deficient for Rb and p27. From these studies, we concluded that the absence of p27 disabled the trigger for an Arf-dependent apoptotic response in Rb-/- tumor cells. This suggests a novel mechanism by which the loss of p27 may impact on tumor development.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Apoptosis / genetics*
Bromocriptine / pharmacology
Cell Cycle / genetics
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cell Division / genetics
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p27
Dopamine / pharmacology
Dopamine Agonists / pharmacology
Fibroblasts / pathology
Mice
Mice, Mutant Strains
Pituitary Gland / drug effects
Pituitary Gland / metabolism
Pituitary Gland / pathology
Pituitary Neoplasms / genetics*
Pituitary Neoplasms / pathology
Retinoblastoma Protein / genetics*
Retinoblastoma Protein / metabolism
Signal Transduction
Tumor Suppressor Protein p14ARF / genetics
Tumor Suppressor Protein p14ARF / metabolism
Tumor Suppressor Proteins / deficiency
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism*

Substances

Cdkn1b protein, mouse
Cdkn2a protein, mouse
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p16
Dopamine Agonists
Retinoblastoma Protein
Tumor Suppressor Protein p14ARF
Tumor Suppressor Proteins
Cyclin-Dependent Kinase Inhibitor p27
Bromocriptine
Dopamine