Tamoxifen modulates apoptotic pathways in primary endometrial cell cultures

Citation
R. Stackievicz et al., Tamoxifen modulates apoptotic pathways in primary endometrial cell cultures, CLIN CANC R, 7(2), 2001, pp. 415-420
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
2
Year of publication
2001
Pages
415 - 420
Database
ISI
SICI code
1078-0432(200102)7:2<415:TMAPIP>2.0.ZU;2-7
Abstract
Clinical data indicate that tamoxifen (TAM) therapy may cause an increased risk of endometrial pathology in postmenopausal but not in premenopausal wo men. Molecular mechanisms of the uterotrophic activity of TAM have not been clearly established nor its relevance to apoptosis in endometrial cells, T he present study was implemented to evaluate the apoptotic effect of TAM on primary endometrial cell cultures in the presence or absence of steroid ho rmones (SHs), A total of 14 primary endometrial cell cultures were establis hed and maintained both with and without SHs. Cell cultures were treated fo r 24 h with either 20 muM TAM or 10 nM estradiol, Apoptotic cells presented in a pre-G(1) peak and the expression of bcl-2 were studied using flow cyt ometry, All endometrial cell cultures maintained in a SH-containing environ ment, except one, responded to TAM by a significant increase (P = 0.03) in the pre-G(1) cell fraction, indicating a proapoptotic effect. A significant (P = 0.03) reduction in the pre-G(1) peak equivalent to an antiapoptotic r esponse was observed in 6 of 13 cell cultures maintained in a SH-deficient environment. In 4 of 10 cell cultures evaluated in both media, the pre-G(1) population was medium dependent, In 8 of 10 cultures evaluated for Bc12 le vels, no trend was found in either media, but a dependency on SH content wa s observed, Comparison between effects of TAM and estradiol demonstrated id entical trends, regardless of the menstrual phase or SH content in cell env ironments. These results suggest that TAM acts as an estrogen agonist on en dometrial tissue in both environments. We conclude that TAM modulates apopt otic pathways in primary endometrial cell cultures. The SH content in the c ell environment influences the apoptotic effect of TAM and determines the p ropensity for a cell to undergo apoptosis or, on the contrary, to resist ap optotic death in response to TAM treatment. This is in concordance with the observed clinical risk of endometrial pathologies in postmenopausal versus premenopausal women.