Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

T. M. Goepfert, M. Mccarthy, F. S. Kittrell, C. Stephens, R. L. Ullrich, B. R. Brinkley, D. Medina

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2221-2229
Number of pages9
JournalFASEB Journal
Volume14
Issue number14
StatePublished - 2000

Fingerprint

Chromosomal Instability
aneuploidy
Aneuploidy
Null Lymphocytes
Chromosomes
breasts
Progesterone
Tumors
progesterone
Breast
epithelial cells
Epithelial Cells
chromosomes
chromosome number
cells
Neoplasms
Cells
centrosomes
Centrosome
neoplasms

Keywords

  • Aneuploidy
  • Centrosomes
  • Estrogen
  • Steroid hormone

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Goepfert, T. M., Mccarthy, M., Kittrell, F. S., Stephens, C., Ullrich, R. L., Brinkley, B. R., & Medina, D. (2000). Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells. FASEB Journal, 14(14), 2221-2229.

Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells. / Goepfert, T. M.; Mccarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

In: FASEB Journal, Vol. 14, No. 14, 2000, p. 2221-2229.

Research output: Contribution to journalArticle

Goepfert, TM, Mccarthy, M, Kittrell, FS, Stephens, C, Ullrich, RL, Brinkley, BR & Medina, D 2000, 'Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells', FASEB Journal, vol. 14, no. 14, pp. 2221-2229.
Goepfert TM, Mccarthy M, Kittrell FS, Stephens C, Ullrich RL, Brinkley BR et al. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells. FASEB Journal. 2000;14(14):2221-2229.
Goepfert, T. M. ; Mccarthy, M. ; Kittrell, F. S. ; Stephens, C. ; Ullrich, R. L. ; Brinkley, B. R. ; Medina, D. / Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells. In: FASEB Journal. 2000 ; Vol. 14, No. 14. pp. 2221-2229.
@article{be9f1f9b5ea84e85a259bff660ee576b,
title = "Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells",
abstract = "Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70{\%} of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40{\%} aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.",
keywords = "Aneuploidy, Centrosomes, Estrogen, Steroid hormone",
author = "Goepfert, {T. M.} and M. Mccarthy and Kittrell, {F. S.} and C. Stephens and Ullrich, {R. L.} and Brinkley, {B. R.} and D. Medina",
year = "2000",
language = "English (US)",
volume = "14",
pages = "2221--2229",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "14",

}

TY - JOUR

T1 - Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

AU - Goepfert, T. M.

AU - Mccarthy, M.

AU - Kittrell, F. S.

AU - Stephens, C.

AU - Ullrich, R. L.

AU - Brinkley, B. R.

AU - Medina, D.

PY - 2000

Y1 - 2000

N2 - Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

AB - Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

KW - Aneuploidy

KW - Centrosomes

KW - Estrogen

KW - Steroid hormone

UR - http://www.scopus.com/inward/record.url?scp=0033746030&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033746030&partnerID=8YFLogxK

M3 - Article

VL - 14

SP - 2221

EP - 2229

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 14

ER -