English, MA, Hughes, SV, Kane, KF et al. (3 more authors) (2000) Oestrogen inactivation in the colon: analysis of the expression and regulation of 17β-hydroxysteroid dehydrogenase isozymes in normal colon and colonic cancer. British Journal of Cancer, 83 (4). 550 - 558. ISSN 0007-0920
Abstract
Epidemiological data suggest that oestrogen contributes to the aetiology of colonic cancer. Furthermore, recent studies have suggested that local hormone metabolism may play a key role in determining colonic responsiveness to oestrogen. To further clarify this mechanism we have characterized the expression and regulation of isozymes of 17β-hydroxysteroid dehydrogenase (17β-HSD) in vitro and in situ. Immunohistochemistry was used to confirm expression of the type 2 and 4 isozymes of 17β-HSD (17β-HSD2 and 4) in normal colonic epithelial cells. Parallel studies suggested that both isozymes were abnormally expressed in colonic tumours and this was confirmed by Western blot analyses. Abnormal expression of 17β-HSD2 and 4 proteins was also observed in Caco-2, HT-29 and SW620 colonic cancer cell lines, although the overall pattern of oestrogen metabolism in these cells was similar to that seen in primary colonic mucosal tissue. The predominant activity (conversion of oestradiol to oestrone) was highest in Caco-2 > SW620 > HT-29, which correlated inversely with the rate of proliferation of the cell lines. Regulatory studies using SW620 cells indicated that the most potent stimulator of oestradiol to oestrone inactivation was the antiproliferative agent 1,25-dihydroxyvitamin D3 (1,25D3), whilst oestradiol itself inhibited 17β-HSD activity. Both oestradiol and 1,25D3 decreased mRNA for 17β-HSD2 and 4. Data indicate that the high capacity for inactivation of oestrogens in the colon is associated with the presence of 17β-HSD2 and 4 in epithelial cells. Abnormal expression of both isozymes in colonic cancer cells and the stimulation of oestrogen inactivation by the antiproliferative agent 1,25D3 highlights a possible role for 17β-HSD isozymes as modulators of colonic cell proliferation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2000, English, MA, Hughes, SV, Kane, KF, Langman, MJS, Stewart, PM and Hewison, M. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial ShareAlike (CC BY-NC-SA 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, provided the original work is properly cited, the use is non-commercial and any derivative works are licensed under the same terms. |
Keywords: | 1,25-Dihydroxyvitamin D3; 17β-hydroxysteroid dehydrogenase; Colonic cancer; Oestradiol; Oestrone |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Medicine & Health Faculty Office (Leeds) > Faculty Office Functions (FOMH) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Nov 2014 12:26 |
Last Modified: | 04 Nov 2017 16:21 |
Published Version: | http://dx.doi.org/10.1054/bjoc.2000.1324 |
Status: | Published |
Publisher: | Cancer Research UK |
Identification Number: | 10.1054/bjoc.2000.1324 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:81073 |