Selective Estrogen Receptor Modulators

Abstract

ABSTRACT

Identification of target genes in breast cancer cells directly regulated by the SRC-3/AIB1 coactivator

“…To validate our approach, the ability of ER␣ and SRC-3 ChIP-based assays to detect a known SRC-3 target gene (pS2͞trefoil factor 1; refs. 30 and 31) as well as several known E2͞ER target genes [GREB1 (32), NRIP1 (16)(17)(18)(19), CYP1B1 (15,33), and LY6E (18,20)] was determined. Q-PCR using primers flanking known EREs (Table 2) demonstrated concordant patterns of E2-stimulated interaction of ER␣ (Fig.…”

“…To this end, RNA profiling and bioinformatic approaches have been used to investigate the molecular pathways by which ER ligands affect breast cancer cells (15)(16)(17)(18)(19)(20), and it is clear that ER target genes are subject to diverse modes of regulation. Although this is partially due to different modes of ER interaction with DNA (21), it is expected that coactivators contribute significantly to this diversity (7,8).…”

Antiestrogens: structure-activity relationships and use in breast cancer treatment

“…Indeed, tamoxifen regulates transcription of subsets of estrogen target genes in endometrial carcinoma cell lines (Ishikawa, ECC-1) and also in ER+ breast cancer cell lines (MCF-7, ZR-75-1), in addition to altering expression of sets of genes apparently not regulated by estradiol via mechanisms that remain to be clarified (Shang & Brown 2002, Frasor et al . 2004, Scafoglio et al .…”

Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways: implications for cell proliferation

“…Thus, one interpretation is that increased signaling through growth factor pathways, including EGF-R, c-erbB2, and c-Src reduces the reliance on estrogen-sensitive proliferation, or may even make such pathways irrelevant in breast cancer cells. It should be noted, however, that tamoxifen is not a 'pure' antiestrogen, and that some genes are still stimulated in the presence of the drug, including those increased by E2 as well as those stimulated only by tamoxifen (Frasor et al, 2004).…”

“…Interestingly, experiments with several pharmacological inhibitors as well as dominant-negative signaling molecules suggest that the MAPK, PI3K, c-Src and STAT pathways all play critical roles in mediating both steroid and growth factor stimulation of cancer cells (Castoria et al, 1999(Castoria et al, , 2001Yue et al, 2002;Kloth et al, 2003;Stoica et al, 2003;Yamashita et al, 2003). Both steroids and growth factors stimulate expression of several genes critical for cell cycle progression, including cyclin D1, cyclin E, and cdk inhibitors p21 and p27, and ongoing expression profiling of breast cancer cells and breast tumors may provide some information on larger subsets of genes that are common for both steroid and growth factorstimulated growth (Sotiriou et al, 2003;Frasor et al, 2004). …”