Alteration of p53 damage response by tamoxifen treatment.
Hormone therapy is often used in association with chemotherapy in the treatment of estrogen-responsive breast cancers. By using breast adenocarcinoma cell lines, we show that antiestrogen treatment leads to a dramatic decrease of p53 protein levels. This effect leads to a loss of wild-type p53 response to genotoxic treatment. This inhibition is assessed by the lack of p53 protein accumulation and the loss of the p53-dependent induction of p21(WAF1/CIP1) expression. Given that the effects of several anticancer agents are mediated through DNA damage, these observations suggest that antiestrogen treatment could modulate cellular response to chemotherapeutic agents.
Guillot
C
C
INSERM U453, and Unité d'Oncologie Moléculaire, Centre Léon Bérard, 28 rue Laënnec, 69008 Lyon, France.
Falette
N
N
Courtois
S
S
Voeltzel
T
T
Garcia
E
E
Ozturk
M
M
Puisieux
A
A
D004249:DNA Damage / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D004965:Estrogen Antagonists; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen; D004958:Estradiol