Parathyroid hormone-related protein secretion is inhibited by oestradiol and stimulated by antioestrogens in KPL-3C human breast cancer cells.
We recently established a human breast cancer cell line, KPL-3C, from a breast cancer patient with humoral hypercalcaemia. This cell line possesses oestrogen receptor (ER) and secretes parathyroid hormone-related protein (PTHrP) into medium. To investigate the effects of oestrogen and antioestrogens on PTHrP secretion, KPL-3C cells were cultured for 48 h in an oestrogen-eliminated medium with 17beta-oestradiol (E2), tamoxifen (TAM) and/or a pure antioestrogen, ICI182,780 (ICI), and PTHrP secretion was measured using an immunoradiometric assay. The effects of these agents on cell cycle progression were also studied using flow cytometry. E2 (1-100 nM) significantly inhibited PTHrP secretion, whereas both TAM (0.1-10 microM) and ICI (1-100 nM) significantly stimulated it. These effects were completely blocked by the simultaneous addition of 1 nM E2 to the medium. At the same time, E2 significantly increased the percentage of cells during the S and G2/M phases, whereas both antioestrogens significantly increased the percentage of cells during the G0/G1 phase. Again, these cytostatic effects were completely reversed by the addition of E2. These findings indicate that antioestrogens inhibit the growth of ER-positive breast cancer cells but may stimulate PTHrP secretion and that these effects may be mediated by ER.
Kurebayashi
J
J
Department of Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, Japan.
Sonoo
H
H
D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D002453:Cell Cycle; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis; D013268:Stimulation, Chemical; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol