Mechanisms of 17-beta-estradiol regulation of the proto-oncogene Bcl-2 in MCF-7 human breast cancer cells.

In the present studies, the mechanisms of estrogen regulation of Bcl-2 were investigated by analyzing the expression of different Bcl-2 promoter-driven constructs stably transfected into MCF-7 cells. An approximately 1.7 kilobase (kb) sequence which directed estrogen-dependent regulation of Bcl-2 expression in these stable MCF-7 clones was identified. Another agent which may play a role in the regulation of Bcl-2 expression is the tumour suppressor gene, p53. We investigated the effects of various mutant p53 proteins and low levels of p53 on Bcl-2 expression in MCF-7 cells. Neither MCF-7/E6 cells expressing virtually undetectable levels of p53 nor MCF-7/173L cells expressing a DNA binding domain mutant p53, showed altered E2-mediated induction of Bcl-2 mRNA or protein levels. However, MCF-7 cells expressing a truncated mutant p53 protein (Delta291) resulted in a dramatic decrease in Bcl-2 protein levels, but not mRNA levels, upon E2 treatment. These results suggest that a p53 protein lacking a carboxy-terminus may cooperate with E2 post-transcriptionally to negatively regulate Bcl-2 levels in MCF-7 human breast cancer cells. (Abstract shortened by UMI.)

Grantor dc:publisher

University of Ottawa (Canada)

Year dc:date

2009

Author dc:creator

• Kushwaha, Neena.

Contributors dc:contributor

• Pratt, Christine,

• Biology, Molecular.

Identifier

Source: Masters Abstracts International, Volume: 40-05, page: 1198.
9780612660663
http://dx.doi.org/10.20381/ruor-11230

OAI identifier oai:identifier

oai:ruor.uottawa.ca:10393/6361