Cell proliferation and death of estrogen sensitive (breast cancer) cells

Estrogenic compounds can induce cell proliferation and cell death. This is important in the development and treatment of (breast) cancer.

Promovendus NM (Nynke) Evers MSc
Promotor JP (John) Groten IMCM (Ivonne) Rietjens
Copromotor dr AGH Ederveen
Organisatie Wageningen University, Sub-department of Toxicology

vr 13 juni 2014 13:30 tot 15:00

Locatie Auditorium, building number 362
Generaal Foulkesweg 1
6703 BG Wageningen

Estrogen can bind to two different estrogen receptors (ER). Binding to ERα stimulates cell proliferation. Binding to ERβ counteracts effects of ERα. In this research the T47D-ERβ breast cancer cell model was used in which ERα/ERβ ratios present in different tissues can be mimicked. Especially the ERα/ERβ ratio in the cell and receptor preference of estrogenic compounds determine whether cell proliferation or cell death is stimulated.

There is mechanistic evidence that endocrine therapy for individuals with ER-positive breast cancer can be further personalized by taking the ERα/ERβ ratio into account.
Nynke Evers

Effects of breast cancer drug tamoxifen

The importance of coregulators and effects of breast cancer drug tamoxifen, which in the body is converted to the more active form 4-hydroxytamoxifen, were also investigated.
In the T47D-ERβ model 4-hydroxytamoxifen can stimulate cell proliferation or apoptosis; 4-hydroxytamoxifen counteracts ERα if (cancer) cells contain relatively much ERα and little ERβ. This could be used to investigate how (cancer) cells will react to the drug.