In vivo stimulation by tamoxifen of cathepsin D RNA level in breast cancer.
We have previously shown that 3 weeks of treatment with tamoxifen, of patients with primary breast carcinomas, increased cytosolic cathepsin D protein in oestrogen receptor (ER) positive tumours [Maudelonde et al., Cancer 1989, 63, 1265-1270]. In order to investigate the mechanism of this increase and to eliminate a transient flare-up effect, we semi-quantified cathepsin D RNA levels by in situ hybridisation in 32 breast carcinomas from patients treated with tamoxifen for 3 weeks prior to surgery and in 35 breast cancer patients receiving no tamoxifen. We found that tamoxifen increased cathepsin D RNA level regardless of the ER status of the tumours. In ER positive tumours, tamoxifen increased the cathepsin D RNA level to the same extent as cytosolic cathepsin D protein but not in ER negative tumours. The induction of cathepsin D RNA by tamoxifen in ER positive tumours was probably due to its agonist activity, also observed in vitro in breast cancer cell lines. These results suggest that the cathepsin D gene is inducible by oestrogens in ER positive breast cancer as it is in breast cancer cell lines.
Institut National de la Santé et de la Recherche Médicale, Unité Hormones et Cancer (U 148), Montpellier, France.
T
T
Maudelonde
C
C
Escot
P
P
Pujol
P
P
Rouanet
A
A
Defrenne
J P
JP
Brouillet
H
H
Rochefort
D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D002402:Cathepsin D / Q000819:agonists / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*
D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D013629:Tamoxifen; D002402:Cathepsin D