Expression of Selected Aurora A Kinase Substrates in Solely Estrogen-induced Ectopic Uterine Stem Cell Tumors in the Syrian Hamster Kidney

  • Adrianne E. Hontz
  • Sara A. Li
  • Jeffrey L. Salisbury
  • Wilma L. Lingle
  • Jonathan J. Li
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)


Sustained over-expression of Aurora A (AurA), centrosome amplification, chromosomal instability, and aneuploidy are salient features that occur in high frequency in human breast premalignant stages and in primary ductal breast cancer (BC), as well as in 17β-estradiol (E2)-induced oncogenesis in animal models. We have reported that AurA/B protein expression increases 8.7-and 4.6-fold, respectively, in primary E2-induced male Syrian hamster uterine stem cell-like tumors of the kidney (EUTK) when compared with cholesterol-treated control kidneys. Upon a 10-day E2-withdrawal or coadministration of tamoxifen citrate, a 78–79% and 81–64% reduction in AurA/B protein expression, respectively, were observed in primary tumors when compared with tumors from animals continuously exposed to E2. These data indicate that AurA/B expression is regulated by estrogens via estrogen receptor a. To determine whether this E2-induced over-expression of the Aur kinases may contribute to the alterations observed during oncogenesis via their phosphorylation of specific substrates, we analyzed the protein expression of histone H3 and targeting protein for Xklp2 (TPX2). Histone H3 and TPX2 were significantly over-expressed 3.7- and 1.6-fold, respectively, in E2-induced tumors when compared with cholesterol-treated control kidney samples. Immunohistochemistry revealed that TPX2 protein expression was essentially confined to tumor foci cells. Collectively, these data indicate that over-expression of AurA/B is under estrogen control and that the deregulation of Aur kinase protein substrates is implicated in eliciting the alterations observed during oncogenesis.


Syrian Hamster Aurora Kinase Tumor Focus Centrosome Amplification Sporadic Breast Cancer 
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  1. 1.
    Hortobagyi GN, de la Garza Salazar J, Pritchard K, et al. (2005) The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer, 6, 391–401.PubMedCrossRefGoogle Scholar
  2. 2.
    Bilimoria MM, Morrow M (1995) The woman at increased risk for breast cancer: evaluation and management strategies. CA Cancer J Clin, 45, 263–78.PubMedCrossRefGoogle Scholar
  3. 3.
    Li SA, Xue Y, Xie Q, et al. (1994) Serum and tissue levels of estradiol during estrogen-induced renal tumorigenesis in the Syrian hamster. J Steroid Biochem Mol Biol, 48, 283–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Gonzalez A, Oberley TD, Li JJ (1989) Morphological and immunohistochemical studies of the estrogen-induced Syrian hamster renal tumor: probable cell of origin. Cancer Res, 49, 1020–8.PubMedGoogle Scholar
  5. 5.
    Li JJ, Weroha SJ, Davis MF, et al. (2001) ER and PR in renomedullary interstitial cells during Syrian hamster estrogen-induced tumorigenesis: evidence for receptor-mediated oncogenesis. Endocrinology, 142, 4006–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Papa D, Li SA, Li JJ (2003) Comparative genomic hybridization of estrogen-induced ectopic uterine-like stem cell neoplasms in the hamster kidney: nonrandom chromosomal alterations. Mol Carcinog, 38, 97–105.PubMedCrossRefGoogle Scholar
  7. 7.
    Escot C, Theillet C, Lidereau R, et al. (1986) Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. Proc Natl Acad Sci USA, 83, 4834–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Whittaker JL, Walker RA, Varley JM (1986) Differential expression of cellular oncogenes in benign and malignant human breast tissue. Int J Cancer, 38, 651–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Walker RA, Cowl J (1991) The expression of c-fos protein in human breast. J Pathol, 163, 323–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Tiniakos DG, Scott LE, Corbett IP, et al. (1994) Studies of c-jun oncogene expression in human breast using a new monoclonal antibody, NCL-DK4. J Pathol, 172, 19–26.PubMedCrossRefGoogle Scholar
  11. 11.
    Liao DZ, Hou X, Bai S, et al. (2000) Unusual deregulation of cell cycle components in early and frank estrogen-induced renal neoplasias in the Syrian hamster. Carcinogenesis, 21, 2167–73.PubMedCrossRefGoogle Scholar
  12. 12.
    Li JJ, Hou X, Banerjee SK, et al. (1999) Overexpression and amplification of c-myc in the Syrian hamster kidney during estrogen carcinogenesis: a probable critical role in neoplastic transformation. Cancer Res, 59, 2340–6.PubMedGoogle Scholar
  13. 13.
    Tanaka T, Kimura M, Matsunaga K, et al. Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast. Cancer Res, 59, 2041–4.Google Scholar
  14. 14.
    Carmena M, Earnshaw WC (2003) The cellular geography of aurora kinases. Nat Rev Mol Cell Biol, 4, 842–54.PubMedCrossRefGoogle Scholar
  15. 15.
    Dutertre S, Descamps S, Prigent C (2002) On the role of aurora-A in centrosome function. Oncogene, 21, 6175–83.PubMedCrossRefGoogle Scholar
  16. 16.
    Andrews PD, Knatko E, Moore WJ, Swedlow JR (2003) Mitotic mechanics: the auroras come into view. Curr Opin Cell Biol, 15, 672–83.PubMedCrossRefGoogle Scholar
  17. 17.
    Ducat D, Zheng Y (2004) Aurora kinases in spindle assembly and chromosome segregation. Exp Cell Res, 301, 60–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Meraldi P, Honda R, Nigg EA (2004) Aurora kinases link chromosome segregation and cell division to cancer susceptibility. Curr Opin Genet Dev, 14, 29–36.PubMedCrossRefGoogle Scholar
  19. 19.
    Li JJ, Li SA (2006) Mitotic kinases: the key to duplication, segregation, and cytokinesis errors, chromosomal instability, and oncogenesis. Pharmacol Ther, 111, 974–84.PubMedCrossRefGoogle Scholar
  20. 20.
    Van Hooser A, Goodrich DW, Allis CD, et al. (1998) Histone H3 phosphorylation is required for the initiation, but not maintenance, of mammalian chromosome condensation. J Cell Sci, 111 (Part 23), 3497–506.PubMedGoogle Scholar
  21. 21.
    Eyers PA, Erikson E, Chen, et al. (2003) A novel mechanism for activation of the protein kinase Aurora A. Curr Biol, 13, 691–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kufer TA, Sillje HH, Korner R, et al. (2002) Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol, 158, 617–23.PubMedCrossRefGoogle Scholar
  23. 23.
    Li JJ, Weroha SJ, Lingle WL, et al. (2004) Estrogen mediates Aurora-A overexpression, centrosome amplification, chromosomal instability, and breast cancer in female ACI rats. Proc Natl Acad Sci USA, 101, 18123–8.PubMedCrossRefGoogle Scholar

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© Springer 2008

Authors and Affiliations

  • Adrianne E. Hontz
    • 1
  • Sara A. Li
    • 1
  • Jeffrey L. Salisbury
    • 2
  • Wilma L. Lingle
    • 3
  • Jonathan J. Li
    • 1
  1. 1.Department of PharmacologyUniversity of Kansas University Medical CenterKansas CityUSA
  2. 2.Tumor Biology ProgramMayo ClinicRochesterUSA
  3. 3.Departmental Laboratory of Medicine and PathologyMayo Clinic FoundationRochesterUSA

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