Expression of p53 and markers for apoptosis in breast tissue during long-term hormone therapy in cynomolgus monkeys.
OBJECTIVE
The purpose of this study was to analyze the expression of p53 and markers for apoptosis in breast tissue during long-term hormone therapy in cynomolgus monkeys.


METHODS
Sixty oophorectomized macaques were randomized to receive tibolone, conjugated equine estrogens (CEE), CEE+medroxyprogesterone acetate (MPA), or no hormonal treatment. Breast tissue was collected at necropsy after 2 years, and stained for p53, p21, and cleaved caspase-3.


RESULTS
Differences were seen between treatment groups. The expression of p53 and caspase-3 was significantly lower in tibolone-treated animals (P<.01). Levels of p53 and caspase-3 were lower in the combined treatment group (CEE+MPA) when compared to both estrogen only and control groups.


CONCLUSIONS
Alternative regimens for hormonal therapy seem to have different effects on p53 expression and apoptotic activity within the breast. A combined effect of increased proliferation and decreased apoptosis could be one possible mechanism to explain an increased risk for breast cancer.
Conner
Peter
P
Department of Obstetrics, Karolinska Hospital, Stockholm, Sweden and Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA. peter.conner@ks.se
Register
Tom C
TC
Skoog
Lambert
L
Tani
Edneia
E
von Schoultz
Bo
B
Cline
J Mark
JM
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004967:Estrogens / Q000008:administration & dosage / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008321:Mammary Glands, Animal / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000627:therapeutic use; D009652:Norpregnenes / Q000008:administration & dosage / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D015415:Biomarkers; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004338:Drug Combinations; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D016159:Tumor Suppressor Protein p53; D017258:Medroxyprogesterone Acetate; D053148:Caspase 3; D020169:Caspases; C027385:tibolone