title: Loss of anti-mitotic effects of Bcl-2 with retention of anti-apoptotic activity during tumor progression in a mouse model.
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.
authors.affiliation: Department of Medicine, University of Maryland Medical School, Baltimore 21201, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Furth
authors.forename: U
authors.initials: U
authors.lastname: Bar-Peled
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Lewis
authors.forename: R
authors.initials: R
authors.lastname: Laucirica
authors.forename: R
authors.initials: R
authors.lastname: Jäger
authors.forename: H
authors.initials: H
authors.lastname: Weiher
authors.forename: R G
authors.initials: RG
authors.lastname: Russell
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2