Premium
Poster Sessions CP01: Genomics and Proteomics. Global gene chip analysis of estrogen and tamoxifen‐regulated genes in the rat cerebral cortex
Author(s) -
Dhandapani K. M.,
Wade F. M.,
De Sevilla L.,
Mahesh V. B.,
Brann D. W.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.30.x
Subject(s) - tamoxifen , biology , gene expression , gene , neuroplasticity , neuroprotection , neuroscience , estrogen receptor , estrogen , synaptic plasticity , endocrinology , genetics , cancer , receptor , breast cancer
The ovarian steroid hormone, 17β‐estradiol (17β‐E2), and selective estrogen receptor modulators (SERMs), such as tamoxifen, have recently been implicated in regulating synaptic plasticity and in the protection of the brain against neurodegenerative diseases such as stroke and Alzheimer's disease. Although the mechanisms of these actions remain poorly understood, changes in gene expression are hypothesized to be involved in these processes. To address this issue, we identified genes that were regulated by physiological doses of 17β‐E2 and/or therapeutic doses of tamoxifen in the rat cerebral cortex of ovariectomized female rats. Gene chip analysis was performed using the Affymetrix U34A gene chip, which contains over 8800 genes and ESTs. Experiments were performed in duplicate to insure reproducibility of gene changes. Data analysis revealed 55 genes were similarly up‐regulated by both 17β‐E2 and tamoxifen whereas 61 genes were similarly down‐regulated, as compared to placebo treated animals. Interestingly, a greater number of genes were differentially regulated by 17β‐E2 and tamoxifen. Regulated genes spanned many different gene classes including signal transduction, transcriptional regulation, cell growth and maintenance, developmental processes, and apoptosis. As a whole, these gene changes may provide novel insights into the molecular mechanisms regulating the well‐documented ability of 17β‐E2 and SERMs to induce synaptic plasticity and neuroprotection in the cerebral cortex.