Estrogens and growth factors induce the mRNA of the 52K-pro-cathepsin-D secreted by breast cancer cells.
The estrogen-induced 52K protein secreted by human breast cancer cells is a lysosomal protease recently identified as a pro-cathepsin D by sequencing several cDNA clones isolated from MCF7 cells (Augereau et al., Mol. Endocr.). Using one of these clones, we detected, in MCF7 cells, a 2.2 kb mRNA whose level was rapidly increased 4- to 10-fold by estradiol, but not by other classes of steroids. Other mitogens, such as epidermal growth factor and insulin, also induced the 2.2 kb mRNA in a dose-dependent manner. Induction with epidermal growth factor was as rapid but was 2- to 3-fold lower than with estradiol. Antiestrogens had no effect on the 52K-cathepsin-D mRNA in MCF7 cells, but became estrogen agonists in two antiestrogen-resistant sublines R27 and LY2. The use of transcription and translation inhibitors and nuclear run-on experiments indicate that estradiol enhances transcription of the 52K-cathepsin-D gene in MCF7 cells.
Cavailles
V
V
Unité d'Endocrinologie Cellulaire et Moléculaire, U 148 INSERM, Montpellier, France.
Augereau
P
P
Garcia
M
M
Rochefort
H
H
D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D002402:Cathepsin D / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D007328:Insulin; D013256:Steroids; D013629:Tamoxifen; D004958:Estradiol; D004815:Epidermal Growth Factor; D002402:Cathepsin D