Tamoxifen treatment increases the concentration of 52K-cathepsin D and its precursor in breast cancer tissue.
The pro-cathepsin D of Mr 52,000 is regulated by estrogens via the estrogen receptor (RE) and is secreted by breast cancer cells in vitro. In an attempt to predict the hormone responsiveness of breast cancer in vivo, we have assayed total 52K cathepsin D and its precursor in the primary breast cancer cytosol of 36 patients treated before surgery with 30 mg of tamoxifen daily for 1 to 5 weeks (average, 3 weeks). Compared to a similar control population, total 52K cathepsin D was increased by tamoxifen (P = 0.02) but less so than its precursor (P less than 0.001). Furthermore, 45% of the RE-positive tumors from tamoxifen-treated patients had a higher cathepsin D precursor concentration than the same type of tumor from control patients, or than RE-negative tumors from tamoxifen-treated patients. This 3-week challenge test was probably too short to avoid partial estrogenic activity of tamoxifen (flare) and the authors infer that longer time of treatment would decrease rather than increase the concentration of cathepsin D in the RE-responsive tumors. However, two cancers from patients with relapses after prolonged tamoxifen treatment (greater than 6 months) also had high concentrations of 52K cathepsin D and its precursor. The authors conclude that the concentration of cathepsin D and its precursor in breast cancer cytosol can be increased by short-term tamoxifen treatment, suggesting that these tumors are estrogen responsive.
Maudelonde
T
T
Unité INSERM 148 Hormones et Cancer, Montpellier, France.
Domergue
J
J
Henquel
C
C
Freiss
G
G
Brouillet
J P
JP
Simony
J
J
Pujol
H
H
Rochefort
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D002402:Cathepsin D / Q000096:biosynthesis*; D003600:Cytosol / Q000201:enzymology; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D011987:Receptors, Steroid / Q000032:analysis / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
D004792:Enzyme Precursors; D011987:Receptors, Steroid; D013629:Tamoxifen; D002402:Cathepsin D