Receptor mediated radiosensitivity and DNA repair capacity of hormone dependent breast cancer cells

BackgroundBreast cancers are considered as either hormone-sensitive or hormone-insensitive based on the expression of estrogen receptor (ER) and progesterone receptor (PR). The ER exists in 2 isoforms, ERα and ERβ, with each isoform having distinct biological effects. ERα stimulates cell growth whereas ERβ stimulates apoptosis and acts as a tumor suppressor. The most prevalent breast cancer subtype is the hormone-sensitive breast cancer, which is eligible for hormonal therapy such as Fulvestrant (Faslodex®). Fulvestrant is a synthetic estrogen antagonist which causes degradation of the ER.A recent in vitro study of our research group showed that lymphocytes of ER positive breast cancer patients had higher chromosomal radiosensitivity values while lymphocytes of triple negative breast cancer patients presented with the lowestradiosensitivity values. However, the exact role of the ER in radiosensitivity remains unclear.AimWe aimed to investigate the link between ERα and ERβ and the radiosensitivity of different hormone-sensitive breast cancer cell lines.MethodsThe impact of Fulvestrant on the morphology and proliferation and a possible link with radiosensitivity of breast cancer cells was investigated. Immunofluorescent staining was performed to demonstrate presence and degradation of ERα and ERβ. Two breast cancer cell lines (MCF-7 and MDA-MB-231) were irradiated with various doses of 220 kV X-rays. Subsequently chromosomal damage was evaluated with the micronucleus assay.Results & ConclusionTreatment of hormone-sensitive MCF-7 cells with Fulvestrant resulted in reduced proliferation, no changes in morphology and degradation of ERα. MCF-7 cellsshowed more radiation-induced micronuclei than hormone-insensitive MDA-MB-231cells confirming a higher radiosensitivity in hormone-sensitive breast cancers.BackgroundBreast cancers are considered as either hormone-sensitive or hormone-insensitive based on the expression of estrogen receptor (ER) and progesterone receptor (PR). The ER exists in 2 isoforms, ERα and ERβ, with each isoform having distinct biological effects. ERα stimulates cell growth whereas ERβ stimulates apoptosis and acts as a tumor suppressor. The most prevalent breast cancer subtype is the hormone-sensitive breast cancer, which is eligible for hormonal therapy such as Fulvestrant (Faslodex®). Fulvestrant is a synthetic estrogen antagonist which causes degradation of the ER.A recent in vitro study of our research group showed that lymphocytes of ER positive breast cancer patients had higher chromosomal radiosensitivity values while lymphocytes of triple negative breast cancer patients presented with the lowestradiosensitivity values. However, the exact role of the ER in radiosensitivity remains unclear.AimWe aimed to investigate the link between ERα and ERβ and the radiosensitivity of different hormone-sensitive breast cancer cell lines.MethodsThe impact of Fulvestrant on the morphology and proliferation and a possible link with radiosensitivity of breast cancer cells was investigated. Immunofluorescent staining was performed to demonstrate presence and degradation of ERα and ERβ. Two breast cancer cell lines (MCF-7 and MDA-MB-231) were irradiated with various doses of 220 kV X-rays. Subsequently chromosomal damage was evaluated with the micronucleus assay.Results & ConclusionTreatment of hormone-sensitive MCF-7 cells with Fulvestrant resulted in reduced proliferation, no changes in morphology and degradation of ERα. MCF-7 cellsshowed more radiation-induced micronuclei than hormone-insensitive MDA-MB-231cells confirming a higher radiosensitivity in hormone-sensitive breast cancers.C