Expression of selected Aurora A kinase substrates in solely estrogen-induced ectopic uterine stem cell tumors in the Syrian hamster kidney.
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 17beta-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 alpha. 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.
Hontz
Adrianne E
AE
Department of Pharmacology, University of Kansas University Medical Center, Kansas City, KS, USA.
Li
Sara A
SA
Salisbury
Jeffrey L
JL
Lingle
Wilma L
WL
Li
Jonathan J
JJ
D000818:Animals; D064127:Aurora Kinases; D015153:Blotting, Western; D002369:Castration; D002471:Cell Transformation, Neoplastic; D002784:Cholesterol / Q000008:administration & dosage; D006224:Cricetinae; D004195:Disease Models, Animal; D004958:Estradiol / Q000633:toxicity; D006657:Histones / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D006657:Histones; D010750:Phosphoproteins; D004958:Estradiol; D002784:Cholesterol; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases