Abstract
Bcl-2 is an anti-apoptotic and anti-proliferative protein over-expressed in several different human cancers including breast. Gain of Bcl-2 function in mammary epithelial cells was superimposed on the WAP-TAg transgenic mouse model of breast cancer progression to determine its effect on epithelial cell survival and proliferation at three key stages in oncogenesis: the initial proliferative process, hyperplasia, and cancer. During the initial proliferative process, Bcl-2 strongly inhibited both apoptosis and mitotic activity. However as tumorigenesis progressed to hyperplasia and adenocarcinoma, the inhibitory effects on mitotic activity were lost. In contrast, anti-apoptotic activity persisted in both hyperplasias and adenocarcinomas. These results demonstrate that the inhibitory effect of Bcl-2 on epithelial cell proliferation and apoptosis can separate during cancer progression. In this model, retention of anti-apoptotic activity with loss of anti-proliferative action resulted in earlier tumor presentation.
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Abbreviations
- WAP:
-
whey acidic protein
- TAg:
-
Simian virus 40 large T antigen
- WAP-TAg:
-
a transgenic mouse model of breast cancer progression in which TAg expression is targeted to mammary epithelial cells using the WAP promoter
- DMBA:
-
dimethylbenz(a)anthracene
- H&E:
-
hematoxylin and eosin
- HPF:
-
high power fields
- s.e.m.:
-
standard error of the mean
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Acknowledgements
Supported by National Cancer Institute grant CA-68033 (to PA Furth) and the Veterans Administration Research Service (PA Furth and R Russell). U Bar-Peled was supported in part by a BARD fellowship.
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Furth, P., Bar-Peled, U., Li, M. et al. Loss of anti-mitotic effects of Bcl-2 with retention of anti-apoptotic activity during tumor progression in a mouse model. Oncogene 18, 6589–6596 (1999). https://doi.org/10.1038/sj.onc.1203073
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DOI: https://doi.org/10.1038/sj.onc.1203073
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