p18Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control

Feng Bai, Xin-Hai Pei, Pier Paolo Pandolfi, Yue Xiong

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Inactivation of the Rb-mediated G1 control pathway is a common event found in many types of human tumors. To test how the Rb pathway interacts with other pathways in tumor suppression, we characterized mice with mutations in both the cyclin-dependent kinase (CDK) inhibitor p18Ink4c and the lipid phosphatase Pten, which regulates cell growth. The double mutant mice develop a wider spectrum of tumors, including prostate cancer in the anterior and dorsolateral lobes, with nearly complete penetrance and at an accelerated rate. The remaining wild-type allele of Pten was lost at a high frequency in Pten+/- cells but not in p18+/- Pten+/- or p18-/- Pten+/- prostate tumor cells, nor in other Pten+/- tumor cells, suggesting a tissue- and genetic background-dependent haploinsufficiency of Pten in tumor suppression. p18 deletion, CDK4 overexpression, or oncoviral inactivation of Rb family proteins caused activation of Akt/PKB that was recessive to the reduction of PTEN activity. We suggest that p18 and Pten cooperate in tumor suppression by constraining a positive regulatory loop between cell growth and cell cycle control pathways.

Original languageEnglish
Pages (from-to)4564-4576
Number of pages13
JournalMolecular and Cellular Biology
Volume26
Issue number12
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

Fingerprint

Cell Cycle Checkpoints
Growth
Neoplasms
Haploinsufficiency
Retinoblastoma Protein
Cyclin-Dependent Kinases
Penetrance
Phosphoric Monoester Hydrolases
Prostate
Prostatic Neoplasms
Alleles
Lipids
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

p18Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control. / Bai, Feng; Pei, Xin-Hai; Pandolfi, Pier Paolo; Xiong, Yue.

In: Molecular and Cellular Biology, Vol. 26, No. 12, 01.06.2006, p. 4564-4576.

Research output: Contribution to journalArticle

Bai, Feng ; Pei, Xin-Hai ; Pandolfi, Pier Paolo ; Xiong, Yue. / p18Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 12. pp. 4564-4576.
@article{0280dce03807407fa67c5addfbeff971,
title = "p18Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control",
abstract = "Inactivation of the Rb-mediated G1 control pathway is a common event found in many types of human tumors. To test how the Rb pathway interacts with other pathways in tumor suppression, we characterized mice with mutations in both the cyclin-dependent kinase (CDK) inhibitor p18Ink4c and the lipid phosphatase Pten, which regulates cell growth. The double mutant mice develop a wider spectrum of tumors, including prostate cancer in the anterior and dorsolateral lobes, with nearly complete penetrance and at an accelerated rate. The remaining wild-type allele of Pten was lost at a high frequency in Pten+/- cells but not in p18+/- Pten+/- or p18-/- Pten+/- prostate tumor cells, nor in other Pten+/- tumor cells, suggesting a tissue- and genetic background-dependent haploinsufficiency of Pten in tumor suppression. p18 deletion, CDK4 overexpression, or oncoviral inactivation of Rb family proteins caused activation of Akt/PKB that was recessive to the reduction of PTEN activity. We suggest that p18 and Pten cooperate in tumor suppression by constraining a positive regulatory loop between cell growth and cell cycle control pathways.",
author = "Feng Bai and Xin-Hai Pei and Pandolfi, {Pier Paolo} and Yue Xiong",
year = "2006",
month = "6",
day = "1",
doi = "10.1128/MCB.00266-06",
language = "English",
volume = "26",
pages = "4564--4576",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - p18Ink4c and Pten constrain a positive regulatory loop between cell growth and cell cycle control

AU - Bai, Feng

AU - Pei, Xin-Hai

AU - Pandolfi, Pier Paolo

AU - Xiong, Yue

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Inactivation of the Rb-mediated G1 control pathway is a common event found in many types of human tumors. To test how the Rb pathway interacts with other pathways in tumor suppression, we characterized mice with mutations in both the cyclin-dependent kinase (CDK) inhibitor p18Ink4c and the lipid phosphatase Pten, which regulates cell growth. The double mutant mice develop a wider spectrum of tumors, including prostate cancer in the anterior and dorsolateral lobes, with nearly complete penetrance and at an accelerated rate. The remaining wild-type allele of Pten was lost at a high frequency in Pten+/- cells but not in p18+/- Pten+/- or p18-/- Pten+/- prostate tumor cells, nor in other Pten+/- tumor cells, suggesting a tissue- and genetic background-dependent haploinsufficiency of Pten in tumor suppression. p18 deletion, CDK4 overexpression, or oncoviral inactivation of Rb family proteins caused activation of Akt/PKB that was recessive to the reduction of PTEN activity. We suggest that p18 and Pten cooperate in tumor suppression by constraining a positive regulatory loop between cell growth and cell cycle control pathways.

AB - Inactivation of the Rb-mediated G1 control pathway is a common event found in many types of human tumors. To test how the Rb pathway interacts with other pathways in tumor suppression, we characterized mice with mutations in both the cyclin-dependent kinase (CDK) inhibitor p18Ink4c and the lipid phosphatase Pten, which regulates cell growth. The double mutant mice develop a wider spectrum of tumors, including prostate cancer in the anterior and dorsolateral lobes, with nearly complete penetrance and at an accelerated rate. The remaining wild-type allele of Pten was lost at a high frequency in Pten+/- cells but not in p18+/- Pten+/- or p18-/- Pten+/- prostate tumor cells, nor in other Pten+/- tumor cells, suggesting a tissue- and genetic background-dependent haploinsufficiency of Pten in tumor suppression. p18 deletion, CDK4 overexpression, or oncoviral inactivation of Rb family proteins caused activation of Akt/PKB that was recessive to the reduction of PTEN activity. We suggest that p18 and Pten cooperate in tumor suppression by constraining a positive regulatory loop between cell growth and cell cycle control pathways.

UR - http://www.scopus.com/inward/record.url?scp=33745051551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745051551&partnerID=8YFLogxK

U2 - 10.1128/MCB.00266-06

DO - 10.1128/MCB.00266-06

M3 - Article

C2 - 16738322

AN - SCOPUS:33745051551

VL - 26

SP - 4564

EP - 4576

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 12

ER -