Effects of a progestogen on normal human breast epithelial cell apoptosis in vitro and in vivo

被引:13
作者
Desreux, J
Kebers, F
Noël, A
Francart, D
Van Cauwenberge, H
Heinen, V
Peyrollier, K
Thomas, JL
Bernard, AM
Paris, J
Delansorne, R
Foidart, JM
机构
[1] Univ Liege, Univ Hosp, Lab Tumor & Dev Biol, B-4000 Liege, Belgium
[2] Theramex Labs, Monaco, Monaco
关键词
normal breast; fibroadenoma; breast cancer; apoptosis; progestogen; nomegestrol acetate;
D O I
10.1016/S0960-9776(03)00003-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis. Both the follicular and luteal phases of the menstrual cycle are characterized by proliferation, whereas apoptosis occurs only at the end of the latter phase. In this study, we observed that the withdrawal of a synthetic progestin (nomegestrol acetate or NOMAC), but not continuous treatment with it, induced apoptosis of normal human breast epithelial cells in vitro and in women who applied NOMAC gel to their breasts. Furthermore, this apoptotic response was specific to normal breast cells, since withdrawal of NOMAC did not induce apoptosis of tumoral T47D cells in vitro or of fibroadenoma cells in women. These observations open up new perspectives in the prevention of hyperplasia and breast cancer. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:142 / 149
页数:8
相关论文
共 42 条
[1]   The Bcl-2 protein family: Arbiters of cell survival [J].
Adams, JM ;
Cory, S .
SCIENCE, 1998, 281 (5381) :1322-1326
[2]   REDUCTION IN APOPTOSIS RELATIVE TO MITOSIS IN HISTOLOGICALLY NORMAL EPITHELIUM ACCOMPANIES FIBROCYSTIC CHANGE AND CARCINOMA OF THE PREMENOPAUSAL HUMAN BREAST [J].
ALLAN, DJ ;
HOWELL, A ;
ROBERTS, SA ;
WILLIAMS, GT ;
WATSON, RJ ;
COYNE, JD ;
CLARKE, RB ;
LAIDLAW, IJ ;
POTTEN, CS .
JOURNAL OF PATHOLOGY, 1992, 167 (01) :25-32
[3]   Death receptors: Signaling and modulation [J].
Ashkenazi, A ;
Dixit, VM .
SCIENCE, 1998, 281 (5381) :1305-1308
[4]   INHIBITION BY NOMEGESTROL ACETATE AND OTHER SYNTHETIC PROGESTINS ON PROLIFERATION AND PROGESTERONE-RECEPTOR CONTENT OF T47-D HUMAN BREAST-CANCER CELLS [J].
BOTELLA, J ;
DURANTI, E ;
DUC, I ;
COGNET, AM ;
DELANSORNE, R ;
PARIS, J .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1994, 50 (1-2) :41-47
[5]   SUPPRESSION OF ICE AND APOPTOSIS IN MAMMARY EPITHELIAL-CELLS BY EXTRACELLULAR-MATRIX [J].
BOUDREAU, N ;
SYMPSON, CJ ;
WERB, Z ;
BISSELL, MJ .
SCIENCE, 1995, 267 (5199) :891-893
[6]   APOPTOSIS AND DISEASE [J].
CARSON, DA ;
RIBEIRO, JM .
LANCET, 1993, 341 (8855) :1251-1254
[7]   NOMEGESTROL ACETATE, A CLINICALLY USEFUL 19-NORPROGESTERONE DERIVATIVE WHICH LACKS ESTROGENIC ACTIVITY [J].
CATHERINO, WH ;
JORDAN, VC .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1995, 55 (02) :239-246
[8]   INFLUENCES OF PERCUTANEOUS ADMINISTRATION OF ESTRADIOL AND PROGESTERONE ON HUMAN BREAST EPITHELIAL-CELL CYCLE IN-VIVO [J].
CHANG, KJ ;
LEE, TTY ;
LINARESCRUZ, G ;
FOURNIER, S ;
DELIGNIERES, B .
FERTILITY AND STERILITY, 1995, 63 (04) :785-791
[9]   Effects of hormone replacement therapy on the mammary gland of surgically postmenopausal cynomolgus macaques [J].
Cline, JM ;
Soderqvist, G ;
vonSchoultz, E ;
Skoog, L ;
vonSchoultz, B .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 1996, 174 (01) :93-100
[10]  
CUNHA GR, 1994, CANCER, V74, P1030, DOI 10.1002/1097-0142(19940801)74:3+<1030::AID-CNCR2820741510>3.0.CO