Activation of the human FP prostanoid receptor disrupts mitosis progression and generates aneuploidy and polyploidy

X. B. Chen, John W Regan

Research output: Contribution to journalArticle

Abstract

Studies have shown prostaglandin F (PGF ) to be an endogenous tumor promoter in mouse models of skin carcinogenesis; however, the mechanisms by which PGF affects cell cycle events remain unknown. Here we performed cell cycle analyses on HEK cells stably expressing the human FP receptor and found that treatment with PGF delays mitosis and is associated with an increased expression of cyclin B1 and Cdc2 kinase activity. In addition, multipolar spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF. Defective cytokinesis was also observed which resulted in gross aneuploidy and polyploidy. Expression of dominant negative Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF. This suggests that FP receptor activation of Rho signaling by PGF can interfere with nuclear division. Aneuploidy is associated with genomic instability and may underlie the tumor-promoting properties of PGF .

Original languageEnglish (US)
Pages (from-to)112-121
Number of pages10
JournalCellular and Molecular Life Sciences
Volume63
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Polyploidy
Dinoprost
Aneuploidy
Mitosis
Chemical activation
Cell Cycle
Cells
Cell Nucleus Division
Cyclin B1
Cytokinesis
Genomic Instability
Chromosomes
prostaglandin F2alpha receptor
Carcinogens
Tumors
Skin
Carcinogenesis
Phosphotransferases

Keywords

  • Aneuploidy
  • Cdc2
  • Cell cycle
  • Cyclin B1
  • Cytokinesis
  • FP prostanoid receptor
  • Polyploidy
  • RhoA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

@article{a4df10c6b0ae476ab32d12e838600ee2,
title = "Activation of the human FP prostanoid receptor disrupts mitosis progression and generates aneuploidy and polyploidy",
abstract = "Studies have shown prostaglandin F2α (PGF 2α) to be an endogenous tumor promoter in mouse models of skin carcinogenesis; however, the mechanisms by which PGF2α affects cell cycle events remain unknown. Here we performed cell cycle analyses on HEK cells stably expressing the human FP receptor and found that treatment with PGF2α delays mitosis and is associated with an increased expression of cyclin B1 and Cdc2 kinase activity. In addition, multipolar spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF2α. Defective cytokinesis was also observed which resulted in gross aneuploidy and polyploidy. Expression of dominant negative Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF2α. This suggests that FP receptor activation of Rho signaling by PGF2α can interfere with nuclear division. Aneuploidy is associated with genomic instability and may underlie the tumor-promoting properties of PGF 2α.",
keywords = "Aneuploidy, Cdc2, Cell cycle, Cyclin B1, Cytokinesis, FP prostanoid receptor, Polyploidy, RhoA",
author = "Chen, {X. B.} and Regan, {John W}",
year = "2006",
month = "1",
doi = "10.1007/s00018-005-5303-0",
language = "English (US)",
volume = "63",
pages = "112--121",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",
number = "1",

}

TY - JOUR

T1 - Activation of the human FP prostanoid receptor disrupts mitosis progression and generates aneuploidy and polyploidy

AU - Chen, X. B.

AU - Regan, John W

PY - 2006/1

Y1 - 2006/1

N2 - Studies have shown prostaglandin F2α (PGF 2α) to be an endogenous tumor promoter in mouse models of skin carcinogenesis; however, the mechanisms by which PGF2α affects cell cycle events remain unknown. Here we performed cell cycle analyses on HEK cells stably expressing the human FP receptor and found that treatment with PGF2α delays mitosis and is associated with an increased expression of cyclin B1 and Cdc2 kinase activity. In addition, multipolar spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF2α. Defective cytokinesis was also observed which resulted in gross aneuploidy and polyploidy. Expression of dominant negative Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF2α. This suggests that FP receptor activation of Rho signaling by PGF2α can interfere with nuclear division. Aneuploidy is associated with genomic instability and may underlie the tumor-promoting properties of PGF 2α.

AB - Studies have shown prostaglandin F2α (PGF 2α) to be an endogenous tumor promoter in mouse models of skin carcinogenesis; however, the mechanisms by which PGF2α affects cell cycle events remain unknown. Here we performed cell cycle analyses on HEK cells stably expressing the human FP receptor and found that treatment with PGF2α delays mitosis and is associated with an increased expression of cyclin B1 and Cdc2 kinase activity. In addition, multipolar spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF2α. Defective cytokinesis was also observed which resulted in gross aneuploidy and polyploidy. Expression of dominant negative Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF2α. This suggests that FP receptor activation of Rho signaling by PGF2α can interfere with nuclear division. Aneuploidy is associated with genomic instability and may underlie the tumor-promoting properties of PGF 2α.

KW - Aneuploidy

KW - Cdc2

KW - Cell cycle

KW - Cyclin B1

KW - Cytokinesis

KW - FP prostanoid receptor

KW - Polyploidy

KW - RhoA

UR - http://www.scopus.com/inward/record.url?scp=30744434825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30744434825&partnerID=8YFLogxK

U2 - 10.1007/s00018-005-5303-0

DO - 10.1007/s00018-005-5303-0

M3 - Article

C2 - 16378246

AN - SCOPUS:30744434825

VL - 63

SP - 112

EP - 121

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 1

ER -