Aurora A and B overexpression and centrosome amplification in early estrogen-induced tumor foci in the Syrian hamster kidney: Implications for chromosomal instability, aneuploidy, and neoplasia

Adrianne E. Hontz, Sara Antonia Li, Wilma L. Lingle, Vivian Negron, Amy Bruzek, Jeffrey L Salisbury, Jonathan J. Li

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Abstract

Estrogen-induced Syrian hamster tumors in the kidney represent a useful model to gain insight into the role of estrogens in oncogenic processes. We provided evidence that early tumor foci in the kidney arise from interstitial ectopic uterine-like germinal stem cells, and that early tumor foci and well-established tumors are highly aneuploid (92-94%). The molecular mechanisms whereby estrogens mediate this process are unclear. Here, we report that estrogen treatment induced significant increases in Aurora A protein expression (8.7-fold), activity (2.6-fold), mRNA (6.0-fold), and Aurora B protein expression (4.6-fold) in tumors, compared with age-matched cholesterol-treated kidneys. Immunohistochemistry revealed that this increase in Aurora A and B protein expression was essentially confined to cells within early and large tumor foci at 3.5 and 6 months of estrogen treatment, respectively. Upon estrogen withdrawal or coadministration of tamoxifen for 10 days, a 78% to 79% and 81% to 64% reduction in Aurora A and B expression, respectively, were observed in primary tumors compared with tumors continuously exposed to estrogens. These data indicate that overexpressed Aurora A and B in these tumors are under estrogen control via estrogen receptor a. Aurora A coenriched with the centrosome fraction isolated from tumors in the kidney. Centrosome amplification (number and area/cell) was detected in early tumor foci and large tumors but not in adjacent uninvolved or age-matched control kidneys. Taken together, these data indicate that persistent overexpression of Aurora A and B is under estrogen control, and is coincident with centrosome amplification, chromosomal instability, and aneuploidy, and represent an important mechanism driving tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2957-2963
Number of pages7
JournalCancer Research
Volume67
Issue number7
DOIs
StatePublished - Apr 1 2007

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Centrosome
Chromosomal Instability
Mesocricetus
Aneuploidy
Estrogens
Kidney
Neoplasms
Neoplastic Stem Cells
Tamoxifen
Estrogen Receptors
Carcinogenesis
Cell Count
Immunohistochemistry
Cholesterol

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Aurora A and B overexpression and centrosome amplification in early estrogen-induced tumor foci in the Syrian hamster kidney : Implications for chromosomal instability, aneuploidy, and neoplasia. / Hontz, Adrianne E.; Li, Sara Antonia; Lingle, Wilma L.; Negron, Vivian; Bruzek, Amy; Salisbury, Jeffrey L; Li, Jonathan J.

In: Cancer Research, Vol. 67, No. 7, 01.04.2007, p. 2957-2963.

Research output: Contribution to journalArticle

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abstract = "Estrogen-induced Syrian hamster tumors in the kidney represent a useful model to gain insight into the role of estrogens in oncogenic processes. We provided evidence that early tumor foci in the kidney arise from interstitial ectopic uterine-like germinal stem cells, and that early tumor foci and well-established tumors are highly aneuploid (92-94{\%}). The molecular mechanisms whereby estrogens mediate this process are unclear. Here, we report that estrogen treatment induced significant increases in Aurora A protein expression (8.7-fold), activity (2.6-fold), mRNA (6.0-fold), and Aurora B protein expression (4.6-fold) in tumors, compared with age-matched cholesterol-treated kidneys. Immunohistochemistry revealed that this increase in Aurora A and B protein expression was essentially confined to cells within early and large tumor foci at 3.5 and 6 months of estrogen treatment, respectively. Upon estrogen withdrawal or coadministration of tamoxifen for 10 days, a 78{\%} to 79{\%} and 81{\%} to 64{\%} reduction in Aurora A and B expression, respectively, were observed in primary tumors compared with tumors continuously exposed to estrogens. These data indicate that overexpressed Aurora A and B in these tumors are under estrogen control via estrogen receptor a. Aurora A coenriched with the centrosome fraction isolated from tumors in the kidney. Centrosome amplification (number and area/cell) was detected in early tumor foci and large tumors but not in adjacent uninvolved or age-matched control kidneys. Taken together, these data indicate that persistent overexpression of Aurora A and B is under estrogen control, and is coincident with centrosome amplification, chromosomal instability, and aneuploidy, and represent an important mechanism driving tumorigenesis.",
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