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.
Maudelonde
T
T
Institut National de la Santé et de la Recherche Médicale, Unité Hormones et Cancer (U 148), Montpellier, France.
Escot
C
C
Pujol
P
P
Rouanet
P
P
Defrenne
A
A
Brouillet
J P
JP
Rochefort
H
H
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