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Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism.
There is great concern over the long-term influence of oral contraceptives on the development of breast cancer in women. Oestrogens are known to stimulate the growth of human breast cancer cells, and this laboratory has previously reported (Jeng & Jordan, 1991) that the 19-norprogestin norethind...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1993
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968434/ https://www.ncbi.nlm.nih.gov/pubmed/8494728 |
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author | Catherino, W. H. Jeng, M. H. Jordan, V. C. |
author_facet | Catherino, W. H. Jeng, M. H. Jordan, V. C. |
author_sort | Catherino, W. H. |
collection | PubMed |
description | There is great concern over the long-term influence of oral contraceptives on the development of breast cancer in women. Oestrogens are known to stimulate the growth of human breast cancer cells, and this laboratory has previously reported (Jeng & Jordan, 1991) that the 19-norprogestin norethindrone could stimulate the proliferation of MCF-7 human breast cancer cells. We studied the influence of the 19-norprogestins norgestrel and gestodene compared to a 'non' 19-norprogestin medroxyprogesterone acetate (MPA) on MCF-7 cell proliferation. The 19-norprogestins stimulated proliferation at a concentration of 10(-8) M, while MPA could not stimulate proliferation at concentrations as great as 3 x 10(-6) M. The stimulatory activity of the 19-norprogestins could be blocked by the antioestrogen ICI 164,384, but not by the antiprogestin RU486. Transfection studies with the reporter plasmids containing an oestrogen response element or progesterone response element (vitERE-CAT, pS2ERE-CAT, and PRE15-CAT) were performed to determine the intracellular action of norgestrel and gestodene. The 19-norprogestins stimulated the vitERE-CAT activity maximally at 10(-6) M, and this stimulation was inhibited by the addition of ICI 164,384. MPA did not stimulate vitERE-CAT activity. A single base pair alteration in the palindromic sequence of vitERE (resulting in the pS2ERE) led to a dramatic decrease in CAT expression by the 19-norprogestins, suggesting that the progestin activity required specific response element base sequencing. PRE15-CAT activity was stimulated by norgestrel, gestodene and MPA at concentrations well below growth stimulatory activity. This stimulation could be blocked by RU486. These studies suggest that the 19-norprogestins norgestrel and gestodene stimulate MCF-7 breast cancer cell growth by activating the oestrogen receptor. |
format | Text |
id | pubmed-1968434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1993 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-19684342009-09-10 Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. Catherino, W. H. Jeng, M. H. Jordan, V. C. Br J Cancer Research Article There is great concern over the long-term influence of oral contraceptives on the development of breast cancer in women. Oestrogens are known to stimulate the growth of human breast cancer cells, and this laboratory has previously reported (Jeng & Jordan, 1991) that the 19-norprogestin norethindrone could stimulate the proliferation of MCF-7 human breast cancer cells. We studied the influence of the 19-norprogestins norgestrel and gestodene compared to a 'non' 19-norprogestin medroxyprogesterone acetate (MPA) on MCF-7 cell proliferation. The 19-norprogestins stimulated proliferation at a concentration of 10(-8) M, while MPA could not stimulate proliferation at concentrations as great as 3 x 10(-6) M. The stimulatory activity of the 19-norprogestins could be blocked by the antioestrogen ICI 164,384, but not by the antiprogestin RU486. Transfection studies with the reporter plasmids containing an oestrogen response element or progesterone response element (vitERE-CAT, pS2ERE-CAT, and PRE15-CAT) were performed to determine the intracellular action of norgestrel and gestodene. The 19-norprogestins stimulated the vitERE-CAT activity maximally at 10(-6) M, and this stimulation was inhibited by the addition of ICI 164,384. MPA did not stimulate vitERE-CAT activity. A single base pair alteration in the palindromic sequence of vitERE (resulting in the pS2ERE) led to a dramatic decrease in CAT expression by the 19-norprogestins, suggesting that the progestin activity required specific response element base sequencing. PRE15-CAT activity was stimulated by norgestrel, gestodene and MPA at concentrations well below growth stimulatory activity. This stimulation could be blocked by RU486. These studies suggest that the 19-norprogestins norgestrel and gestodene stimulate MCF-7 breast cancer cell growth by activating the oestrogen receptor. Nature Publishing Group 1993-05 /pmc/articles/PMC1968434/ /pubmed/8494728 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Catherino, W. H. Jeng, M. H. Jordan, V. C. Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. |
title | Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. |
title_full | Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. |
title_fullStr | Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. |
title_full_unstemmed | Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. |
title_short | Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. |
title_sort | norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968434/ https://www.ncbi.nlm.nih.gov/pubmed/8494728 |
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