TY - JOUR
T1 - Mammary carcinogenesis is preceded by altered epithelial cell turnover in transforming growth factor-α and c-myc transgenic mice
AU - Rose-Hellekant, Teresa A.
AU - Wentworth, Kristin M.
AU - Nikolai, Sarah
AU - Kundel, Donald W.
AU - Sandgren, Eric P.
N1 - Funding Information:
Supported in part by the National Institutes of Health (grants K01-RR00145 to T.A.R.-H., R01-CA64843 to E.P.S., and ES09090 ). Regular Articles
PY - 2006/11
Y1 - 2006/11
N2 - Identification of biomarkers that indicate an increased risk of breast cancer or that can be used as surrogates for evaluating treatment efficacy is paramount to successful disease prevention and intervention. An ideal biomarker would be identifiable before lesion development. To test the hypothesis that changes in cell turnover precede mammary carcinogenesis, we evaluated epithelial cell proliferation and apoptosis in mammary glands from transgenic mice engineered to develop mammary cancer due to expression in mammary epithelia of transforming growth factor α (TGF-α) or c-myc. In transgenic glands, before lesion development, epithelial cell turnover was enhanced overall compared with nontransgenic glands, indicating that aberrant cell turnover in normal epithelia may contribute to tumorigenesis. In addition, in tumor-containing glands, proliferation in normal epithelia was higher than in tumor-free transgenic glands, suggesting these cell populations influence one another. Finally, although c-myc glands displayed a uniformly high epithelial cell turnover regardless of age, cell turnover was reduced with aging in nontransgenic and TGF-α mice, indicating that some growth and death regulatory mechanisms remain intact in TGF-α epithelia. These observations support the evaluation of cell turnover as a biomarker of cancer risk and indicator of prevention/treatment efficacy in preclinical models and warrant validation in human breast cancer.
AB - Identification of biomarkers that indicate an increased risk of breast cancer or that can be used as surrogates for evaluating treatment efficacy is paramount to successful disease prevention and intervention. An ideal biomarker would be identifiable before lesion development. To test the hypothesis that changes in cell turnover precede mammary carcinogenesis, we evaluated epithelial cell proliferation and apoptosis in mammary glands from transgenic mice engineered to develop mammary cancer due to expression in mammary epithelia of transforming growth factor α (TGF-α) or c-myc. In transgenic glands, before lesion development, epithelial cell turnover was enhanced overall compared with nontransgenic glands, indicating that aberrant cell turnover in normal epithelia may contribute to tumorigenesis. In addition, in tumor-containing glands, proliferation in normal epithelia was higher than in tumor-free transgenic glands, suggesting these cell populations influence one another. Finally, although c-myc glands displayed a uniformly high epithelial cell turnover regardless of age, cell turnover was reduced with aging in nontransgenic and TGF-α mice, indicating that some growth and death regulatory mechanisms remain intact in TGF-α epithelia. These observations support the evaluation of cell turnover as a biomarker of cancer risk and indicator of prevention/treatment efficacy in preclinical models and warrant validation in human breast cancer.
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U2 - 10.2353/ajpath.2006.050675
DO - 10.2353/ajpath.2006.050675
M3 - Article
C2 - 17071603
AN - SCOPUS:37249020287
SN - 0002-9440
VL - 169
SP - 1821
EP - 1832
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -