Abstract
Xenograft tumours from an oestrogen-dependent human breast cancer cell line MCF-7 have been established and characterised in thymectomised, irradiated female CBA strain mice. There was evidence for selection in xenografts of a subpopulation of MCF-7 cells with an altered pattern of gene expression as measured by mRNA levels compared with the original cells in vitro. Tumorigenicity increased significantly on repeated animal passage but oestrogen dependence was retained. Following injection of the mice with oestrogen, mitosis was induced in the tumour cells with associated increases in thymidine uptake and percentage of cells in S-phase. In accord with these changes, c-myc and p53 expression were increased and TGF-beta was suppressed. Thereafter the expression of the c-myc and p53 genes fell whilst that of the TGF-beta gene was induced as the oestrogenic-stimulus declined. The oestrogen-regulated mRNA pS2 showed a biphasic response to oestrogen and levels declined as the serum oestrogen fell to undetectable levels. This xenograft system demonstrates that changes in transcription of oncogenes, growth factor and oestrogen-regulated genes can be detected in vivo in response to oestrogen. It thus provides an in vivo model for studies of the biochemical and molecular basis for therapeutic manipulation of hormone-sensitive human breast cancer.
Highlights
We report here the characterization of an oestrogenresponsive tumour derived from the MCF-7 human breast carcinoma cell line grown in vivo in female thymectomised and irradiated CBA mice
MCF-7 cells (Soule et al, 1973) were cultured in Nunclon flasks (Nunc, Kamstrup, Denmark), fed regularly with Dulbecco's Modified Eagle Medium (DMEM; Gibco, Paisley, UK) containing phenol red supplemented with 12% fetal calf serum (FCS; Gibco) and maintained in an atmosphere containing 5% CO2 at 37°C
One hundred and forty-five CBA strain mice were injected with MCF-7 cells in this study (Table I)
Summary
Twenty-one day old female mice from an established breeding colony of CBA/Ca strain mice at the Institute of Animal Technology, Western General Hospital, Edinburgh, maintained as described in Hay et al (1985), were anaesthetised with ether and suction thymectomy performed. 200mgkg'I arabinoside C (Pfizer, UK) was injected by the intraperitoneal route and 48 h later the mice were irradiated to a total body dose of 7.50 Gy. Radiation was delivered from an X-ray source (250 kv: 0.3-0.4 Gy min-') with a Thoreus II filter. MCF-7 cells (Soule et al, 1973) were cultured in Nunclon flasks (Nunc, Kamstrup, Denmark), fed regularly with Dulbecco's Modified Eagle Medium (DMEM; Gibco, Paisley, UK) containing phenol red (which has an oestrogenic effect on MCF7 cells) supplemented with 12% fetal calf serum (FCS; Gibco) and maintained in an atmosphere containing 5% CO2 at 37°C.
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