Overexpression and hormonal regulation of pro-cathepsin D in mammary and endometrial cancer.
Pro-cathepsin D is overexpressed in breast cancer cells compared to normal mammary epithelial cells. Moreover, its processing and maturation are altered resulting in increased secretion. In estrogen-responsive breast cancer cell lines such as MCF7 cells and ZR75-1 cells, the 2.2-kb cathepsin D mRNA is accumulated specifically by estrogens and growth factors. Estrogen regulation is mostly transcriptional, while growth factors stabilize the mRNA and act indirectly. In estrogen-receptor-negative cell lines, there is a constitutive high production of cathepsin D mRNA. Moreover in uterine cells, progesterone is the inducer rather than estrogen, indicating the complexity of regulation by steroids, depending on the tissue. The increased production of cathepsin D appears to be correlated with the aggressiveness of the tumour, as shown by retrospective clinical studies, suggesting a role in mammary carcinogenesis.
Rochefort
H
H
Unité Hormones et Cancer (U148), Université de Montpellier, France.
Cavailles
V
V
Augereau
P
P
Capony
F
F
Maudelonde
T
T
Touitou
I
I
Garcia
M
M
D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D002402:Cathepsin D / Q000096:biosynthesis / Q000235:genetics*; D015342:DNA Probes; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000235:genetics
D015342:DNA Probes; D004792:Enzyme Precursors; D004965:Estrogen Antagonists; D004967:Estrogens; D006133:Growth Substances; D012333:RNA, Messenger; C058345:procathepsin D; D002402:Cathepsin D