afimoxifene has been researched along with Osteosarcoma* in 4 studies
4 other study(ies) available for afimoxifene and Osteosarcoma
Article | Year |
---|---|
Down-regulation of epidermal growth factor receptor induced by estrogens and phytoestrogens promotes the differentiation of U2OS human osteosarcoma cells.
In previous studies on HeLa cells we demonstrated estrogen-responsiveness of the epidermal growth factor receptor (EGFR) gene, as 17beta-estradiol (E(2)) and selective estrogen receptor modulators (SERMs) genistein (G), daidzein (D), and 4-hydroxytamoxifen (4OH-T) modulated its transcription in a ligand- and estrogen receptor (ER) isoform-specific way. This study describes further investigations into the role of ERs in mediating the effects induced by E(2) and SERMs on EGFR expression, and the relationship between the actions of ERs and EGFR in U2OS osteosarcoma cells stably expressing ERalpha or ERbeta. Cell number and DNA content determination revealed that E(2), G, and D inhibited proliferation and cell cycle progression and promoted apoptosis in both cell lines. In parallel, changes in cell morphology typical of osteoblast maturation were observed via optical microscopy. Consistently, quantitative PCR and Western blot analysis showed an up-regulation of markers of osteoblast differentiation and bone repair, and a decrease in EGFR expression. The transfection of specific antisense (AS) oligonucleotides strengthened our hypothesis that EGFR reduction caused changes in the proliferation/differentiation pattern comparable to those induced by ER ligands. The link between the ER and EGFR pathways was confirmed by treatment with 4OH-T, which decreased the EGFR level and produced differentiation effects via ERalpha, but induced both EGFR expression and proliferation effects via ERbeta. In conclusion, we show that also in U2OS cells, E(2) and SERMs are able to modulate the expression of the EGFR gene and can affect events strictly controlled by its signaling pathway, such as the maturation of osteoblasts. Topics: Apoptosis; Biomarkers; Cell Cycle; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cell Shape; Down-Regulation; ErbB Receptors; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Genistein; Humans; Isoflavones; Osteoblasts; Osteosarcoma; Phytoestrogens; RNA, Messenger; Selective Estrogen Receptor Modulators; Tamoxifen; Time Factors | 2009 |
Estrogen receptor alpha and beta heterodimers exert unique effects on estrogen- and tamoxifen-dependent gene expression in human U2OS osteosarcoma cells.
The 17beta-estradiol (E2) receptor isoforms [estrogen receptor (ER) alpha and ERbeta] bind E2 and selective ER modulators (SERMs) as homodimers (alpha/alpha or beta/beta) or heterodimers (alpha/beta) to regulate gene expression. Although recent studies have shown that ER homodimers regulate unique sets of E2-responsive genes, little information exists regarding the transcriptional actions of the ERalpha/beta heterodimer. This paper describes the development of a U2OS human osteosarcoma (osteoblast) cell line stably expressing both ERalpha and ERbeta isoforms at a ratio of 1:4, a ratio reported to exist in normal, mature osteoblast cells derived from cancellous bone. The regulation of endogenous genes by E2 and 4-hydroxy-tamoxifen were measured in these cells using gene microarrays and real-time RT-PCR. Both E2 and 4-hydroxy-tamoxifen were shown to regulate unique sets of endogenous genes in the U2OS-ERalpha/beta heterodimer cell line (20% and 27% of total, respectively), compared with all the genes regulated in U2OS-ER homodimer cell lines. Furthermore, two novel E2-regulated genes, retinoblastoma binding protein 1 and 7-dehydrocholesterol reductase, were found to contain estrogen response element-like sequences that directly bind the ERalpha/beta heterodimer. These results suggest that the expression of both ER isoforms, forming functional ERalpha/beta heterodimers, result in unique patterns of gene regulation, many of which are distinct from the genes regulated by the ER homodimers. Topics: Blotting, Western; Carrier Proteins; Cell Line; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Chromatin Immunoprecipitation; Dimerization; Down-Regulation; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Gene Expression Regulation; Humans; Immunoprecipitation; Models, Genetic; Oligonucleotide Array Sequence Analysis; Osteoblasts; Osteosarcoma; Oxidoreductases Acting on CH-CH Group Donors; Promoter Regions, Genetic; Protein Binding; Protein Isoforms; Response Elements; Retinoblastoma-Binding Protein 1; Reverse Transcriptase Polymerase Chain Reaction; Tamoxifen | 2005 |
Overexpression of estrogen receptor in HTB 96 human osteosarcoma cells results in estrogen-induced growth inhibition and receptor cross talk.
Estrogenic effects on the proliferation and differentiated cellular functions of bone cells have been described in vivo and in vitro. In particular, stimulatory effects on the growth rate of osteoblasts have been observed, although these are generally small. In an attempt to produce a more sensitive model for the study of estrogen action in bone, HTB 96 human osteoblast-like osteosarcoma cells, which lack endogenous estrogen receptor (ER), were stably transfected with an expression vector coding for the human ER gene. Several HTB 96 sublines expressing ER protein, detected by ligand binding and immunoassay, were isolated. The ability of 17 beta-estradiol (E2) to induce chloramphenicol acetyltransferase (CAT) activity from a cotransfected reporter vector containing the CAT gene linked to the Xenopus vitellogenin A2 gene estrogen response element demonstrated that the expressed ER was functional. ER continued to be expressed over a 30 week culture period. E2 but not other steroids significantly reduced growth rates and produced an altered morphology in HTB 96 sublines expressing higher levels of ER. The antiestrogen 4-hydroxytamoxifen partially reversed the E2 effect on growth rate. Transient transfection of cells expressing ER with a vector containing the CAT gene linked to the mouse mammary tumor virus long terminal repeat sequence, which contains response elements for the glucocorticoid receptor but not the ER, showed that E2 was able to inhibit CAT induction by dexamethasone. This result suggest that in ER-transfected HTB 9 cells the effects of E2 may result not from direct activation of endogenous genes but instead by transcriptional interference.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Animals; Base Sequence; Cell Division; Chloramphenicol O-Acetyltransferase; Estradiol; Gene Expression Regulation; Genes, Reporter; Genetic Vectors; Humans; Molecular Sequence Data; Osteosarcoma; Receptors, Estrogen; Tamoxifen; Transfection; Xenopus laevis | 1994 |
Steroid receptors in human osteoblast-like cells.
The presence and functions of steroid receptors were evaluated in three human osteosarcoma cell lines (OS1 = SA OS; OS2 = HOS TE 85, and OS3 = MNNG HOS TE 85). The human breast cancer cell line MCF-7 was used as internal control for oestrogen receptors (E2R). High and low affinity sites were characterised. The high affinity sites had a similar dissociation constant in all four cell lines. In contrast, the number of sites per cell was higher in MCF-7 cells. E2 did not significantly modify the number of progesterone receptors (PgR) per cell in any of the osteosarcoma lines. As expected, E2 increased the number of PgR sites per MCF-7 cell. 4-hydroxytamoxifen decreased the growth of MCF-7 cells only. OS1 and OS2 were sensitive only to the highest concentration tested, which produces only non-specific cytotoxic effects. Thus E2R and PgR were found in osteoblast-like cells, but the function of E2R in such cells remains unknown. Topics: Breast Neoplasms; Cell Line; Dose-Response Relationship, Drug; Estrogen Antagonists; Female; Humans; Mitosis; Osteosarcoma; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen | 1990 |