Treatment of neuroblastoma cell line SH-SY5Y with various estrogenic agents cause differential effects on D2-like and ER receptor sub-type gene expression.

B83

Tamoxifen is a selective estrogen receptor modulator (SERM), a class of drugs that mimic or counteract the estrogenic effects. Tamoxifen is also a common chemotherapeutic treatment for ER-positive breast cancer. However, difficulty with some mental functions after chemotherapy, often referred to as "chemo brain" is a common side-effect (i.e. problems include memory and learning, attention and concentration, language and judging spaces and layout when moving about). Therefore, determination of any neuromodulatory events associated with treatment is necessary. . A characteristic that distinguishes SERMs from receptor agonists and antagonists is that their action is different for various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogenic action via activation of estrogen receptor (ER) sub-types ER alpha and/or ER beta. (Ohmichi et al., 2005) D2 - like dopamine receptors participate directly or indirectly with many of the problems associated with chemo brain. Therefore, this study begins to understand the underlying mechanisms that may lead to gene expression changes in the brain during chemotherapy. Treatment of the human neuroblastoma cell line, SH-SY5Y with, 17beta - estradiol (E2), Tamoxifen (Tam) and the GlaxoSmithKline SERM, GSK653580A (GSK SERM; a gift from Dave Jones of GlaxoSmithKline, RTP, NC) for 24 hours. Analysis of isolated total RNA via real-time polymerase chain reaction indicated the following changes in gene expression pattern of D2-like dopamine and ER receptor sub-types: 1) at 10^-9 M, E2 represses gene expression for D₂ dopamine, D₄ dopamine and both ER sub-types; 2) Tam causes significant increases in the gene expression of the D₂ dopamine receptor sub-type but no significant changes occurred for D₄ dopamine, ER alpha or ER beta receptors; and 3) while GSK-SERM caused increases in ER beta gene expression, but minimal dose-dependent response of D2 dopamine receptor, D4 dopamine receptor or ER alpha receptor subtypes. With all treatments, D3 dopamine receptor was undetected. Therefore, these results suggest that SERMs differentially affect gene expression in the brain.