Demonstration of mixed properties of RU486 in progesterone receptor (PR)-transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues
| Autor: | E H Ng, V C-L Lin, E H-L Ng, M G-K Tan, Swee Eng Aw |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
MAPK/ERK pathway
RU486 morphology cell growth p42/p44 MAPK PR-transfected MDA-MB-231 Cancer Research medicine.medical_specialty endocrine system MAP Kinase Signaling System Cellular differentiation Recombinant Fusion Proteins Breast Neoplasms Gonanes Biology Transfection Progesterone Antagonist Focal adhesion Hormone Antagonists Internal medicine Stress Fibers Progesterone receptor medicine polycyclic compounds Tumor Cells Cultured Humans Progesterone Cell Size Focal Adhesions Cell growth Cell Cycle Regular Article Mifepristone Cell cycle Cell biology Enzyme Activation Endocrinology Oncology Female Receptors Progesterone hormones hormone substitutes and hormone antagonists Cell Division medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | Progesterone antagonist RU486 (mifepristone) has been implicated for many anti-neoplastic and obstetrical applications. But the compound has demonstrated undesired agonist-like effect depending on cell, tissue and species studied. Using PR-transfected breast cancer cells MDA-MB-231, this report describes the similarities and differences between progesterone- and RU486-mediated effects on cell growth, cell differentiation and, at the molecular level, on the activation of p44/p42 MAP kinases (MAPK). Like progesterone, RU486 inhibited cells growth by arresting the cells in G0/G1 phase of the cell cycle. In contrast to progesterone that induced cell spreading, RU486 induced a multipolar, stellate morphology. RU486-treated cells showed no increase of stress fibers, nor was there any increase of focal adhesions as progesterone-treated cells did. Furthermore, despite of the fact that both compounds inhibited cell growth, RU486 significantly stimulated the activation of p44/p42 MAP kinases whereas progesterone markedly inhibited the activation. Nonetheless, the effects of RU486 were PR-mediated and RU486 was able to antagonize the effect of progesterone on cell growth and focal adhesion. In conclusion, RU486 can act not only as a progesterone antagonist, a progesterone agonist but also induced morphological and molecular changes that were distinct from progesterone-mediated effects in PR-transfected MDA-MB-231 cells. The non-progesterone-like effect of RU486 may be mediated through a pathway that is different from the progesterone-mediated pathway, or it is the result of a blockade of certain critical step(s) in the progesterone-mediated pathway. In any case, undesired side effects of antiprogestin may create clinical complications. PR-transfected MDA-MB-231 breast cancer cells provide a model for studying the functions of progesterone analogues.© 2001 Cancer Research Campaign http://www.bjcancer.com |
| Databáze: | OpenAIRE |
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