Abstract 808: Endocrine resistance: The influence of stromal-epithelial interaction on intracrine pathways of oestrogen synthesis
| Autor: | Atul Purohit, Carlo Palmieri, Joshua M. Odendaal |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Cancer Research. 72:808-808 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2012-808 |
| Popis: | Resistance to endocrine therapy, both de novo and acquired, poses a significant clinical challenge. Two primary pathways, the aromatase and steroid sulphatase (STS) pathways, exist for the production of estrogenic steroids from androstenedione and DHEAS, respectively. Numerous studies have demonstrated an upregulation of these pathways in breast tumour tissue compared to normal breast tissue. Therapies targeting oestrogenic pathways form the mainstay of the pharmacological approach to breast cancer treatment. The SERM, Tamoxifen, and aromatase inhibitors (AI) such as Letrozole, have shown substantial clinical benefit in hormone-dependent breast cancer patients. Additionally, to date one STS inhibitor has entered clinical trials. Despite this success, a proportion of hormone-receptor positive patients do not respond to hormone therapy with 40% of patients who initially show a response to Tamoxifen relapsing. As little is known about the influence of the tumour microenvironment, particularly stromal-fibroblasts, on these pathways in the development of endocrine resistance, we have examined the influence of stromal-epithelial interactions on the expression of enzymes of steroidogenesis in endocrine resistant cells. Wild type and tamoxifen-resistant MCF-7 breast cancer cells (MCF-7wt and MCF-7TamR, respectively) were indirectly co-cultured with primary fibroblasts derived from breast tumour and reduction mammoplasty samples, using 0.4μm 6-well inserts. Expression levels of 17α-hydroxysteroid dehydrogenase types 1 (17α-HSD1) and 2, (17α-HSD2), aromatase, oestrogen receptor ≤ (ERα) and β, progesterone receptor, steroid sulphatase (STS), and steroid sulphotransferase were assessed basally and in co-culture using RT-PCR. Significantly higher basal expression of STS (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 808. doi:1538-7445.AM2012-808 |
| Databáze: | OpenAIRE |
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