| Title |
Multiple actions of synthetic ‘progestins’ on the growth of ZR-75-1 human breast cancer cells: Anin vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, January 1991
|
| DOI | 10.1007/bf01806369 |
| Pubmed ID | |
| Authors |
Richard Poulin, Denis Baker, Donald Poirier, Fernand Labrie |
| Abstract |
This study was designed to assess the multiple steroid receptor mediated activities of a series of synthetic 'progestins' on breast cancer cell growth, using the human ZR-75-1 cell line which possesses functional estrogen (ER), androgen (AR), and glucocorticoid (GR) receptors as well as progesterone (PgR) receptors. Four 17-hydroxyprogesterone derivatives (chlormadinone acetate, CMA; cyproterone acetate, CPA; medroxyprogesterone acetate, MPA; and megestrol acetate, MGA) and two 19-nortestosterone derivatives (norethindrone, NRE, and norgestrel, NRG) were thus investigated. Based on the requirement of estrogens for PgR-mediated antiproliferative effects and the reversal of PgR-mediated action by insulin, it was found that although all 'progestins' could inhibit ZR-75-1 cell growth through the PgR at low concentrations, the relative contribution of this receptor in cell growth control is highly variable between compounds. The quantitative importance of PgR-mediated inhibition of cell proliferation was inversely related to the amplitude of the androgenic effects induced by the compounds, the AR-mediated effects increasing in the order CPA less than MGA less than CMA less than NRE less than NRG less than MPA. The specificity of these androgenic effects is further supported by their reversal upon addition of the antiandrogen hydroxyflutamide. In addition, the 17-hydroxyprogesterone derivatives, but not the 19-nortestosterone derivatives, had glucocorticoid activities at high (micromolar) concentrations, as shown by reversal of growth inhibition by the antagonist RU486 in the presence of saturating concentrations of 5 alpha-dihydro-testosterone. All 'progestins' tested, except MPA and NRE, also had some antiglucocorticoid activity, NRG being the most potent in this respect. Finally, NRE and NRG exerted a marked mitogenic effect in estrogen-free medium which was clearly mediated through the ER as shown by the competitive reversal of their action by the steroidal antiestrogen EM-139. The present results show that growth measurements of the human breast cancer cells ZR-75-1 permit, with the appropriate steroid additions, the assay of progestin, androgen, estrogen, and glucocorticoid agonistic as well as antagonistic activities of test compounds. The present study shows, somewhat surprisingly, that while the AR is almost completely responsible for the action of MPA at low concentrations, the majority of the action of NRE, NRG, and MGA is also exerted through AR, while the androgenic action of CPA plays a lower role in the growth inhibition induced by this compound.(ABSTRACT TRUNCATED AT 400 WORDS) |
Mendeley readers
The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 5% |
| Unknown | 19 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 25% |
| Professor | 3 | 15% |
| Student > Master | 3 | 15% |
| Professor > Associate Professor | 2 | 10% |
| Student > Ph. D. Student | 1 | 5% |
| Other | 2 | 10% |
| Unknown | 4 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 30% |
| Biochemistry, Genetics and Molecular Biology | 3 | 15% |
| Medicine and Dentistry | 3 | 15% |
| Nursing and Health Professions | 1 | 5% |
| Business, Management and Accounting | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 5 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 December 2018.
All research outputs
#7,454,951
of 22,790,780 outputs
Outputs from Breast Cancer Research and Treatment
#1,658
of 4,655 outputs
Outputs of similar age
#11,911
of 59,444 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#2
of 5 outputs
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