Abstract
Expression of parathyroid hormone-related protein (PTHrP) in breast carcinoma is a frequent cause of the paraneoplastic syndrome of hypercalcemia. In response to treatment with estrogen or tamoxifen, some breast cancer patients also develop a transient hypercalcemia. Therefore, the effect of 17β-estradiol (E2), tamoxifen, or its more potent metabolite, 4-hydroxytamoxifen (OH-tamoxifen), on PTHrP expression in an estrogen receptor (ER)-positive breast carcinoma cell line (MCF-7) was evaluated. E2 increased PTHrP mRNA levels in MCF-7 cells and stimulated PTHrP(1-86) release in a dose-dependent fashion (10-10-10-6 M). Tamoxifen and OH-tamoxifen also stimulated PTHrP release in a concentration-dependent fashion that paralleled their relative ER binding affinities (10-6 or 10-8-10-6 M, respectively). Combined treatment with the partial estrogen agonist, OH-tamoxifen, and E2 decreased E2-stimulated PTHrP secretion in MCF-7 cells to the levels seen with OH-tamoxifen treatment alone. These results suggest that transient estrogen- or tamoxifen-induced hypercalcemia in patients with breast carcinoma may be a PTHrP-mediated effect that is a marker of ER positivity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 849-854 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 251 |
| Issue number | 3 |
| DOIs | |
| State | Published - Oct 29 1998 |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Regulation of parathyroid hormone-related protein expression in MCF-7 breast carcinoma cells by estrogen and antiestrogens. / Funk, Janet L; Wei, Hongbing.
In: Biochemical and Biophysical Research Communications, Vol. 251, No. 3, 29.10.1998, p. 849-854.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of parathyroid hormone-related protein expression in MCF-7 breast carcinoma cells by estrogen and antiestrogens
AU - Funk, Janet L
AU - Wei, Hongbing
PY - 1998/10/29
Y1 - 1998/10/29
N2 - Expression of parathyroid hormone-related protein (PTHrP) in breast carcinoma is a frequent cause of the paraneoplastic syndrome of hypercalcemia. In response to treatment with estrogen or tamoxifen, some breast cancer patients also develop a transient hypercalcemia. Therefore, the effect of 17β-estradiol (E2), tamoxifen, or its more potent metabolite, 4-hydroxytamoxifen (OH-tamoxifen), on PTHrP expression in an estrogen receptor (ER)-positive breast carcinoma cell line (MCF-7) was evaluated. E2 increased PTHrP mRNA levels in MCF-7 cells and stimulated PTHrP(1-86) release in a dose-dependent fashion (10-10-10-6 M). Tamoxifen and OH-tamoxifen also stimulated PTHrP release in a concentration-dependent fashion that paralleled their relative ER binding affinities (10-6 or 10-8-10-6 M, respectively). Combined treatment with the partial estrogen agonist, OH-tamoxifen, and E2 decreased E2-stimulated PTHrP secretion in MCF-7 cells to the levels seen with OH-tamoxifen treatment alone. These results suggest that transient estrogen- or tamoxifen-induced hypercalcemia in patients with breast carcinoma may be a PTHrP-mediated effect that is a marker of ER positivity.
AB - Expression of parathyroid hormone-related protein (PTHrP) in breast carcinoma is a frequent cause of the paraneoplastic syndrome of hypercalcemia. In response to treatment with estrogen or tamoxifen, some breast cancer patients also develop a transient hypercalcemia. Therefore, the effect of 17β-estradiol (E2), tamoxifen, or its more potent metabolite, 4-hydroxytamoxifen (OH-tamoxifen), on PTHrP expression in an estrogen receptor (ER)-positive breast carcinoma cell line (MCF-7) was evaluated. E2 increased PTHrP mRNA levels in MCF-7 cells and stimulated PTHrP(1-86) release in a dose-dependent fashion (10-10-10-6 M). Tamoxifen and OH-tamoxifen also stimulated PTHrP release in a concentration-dependent fashion that paralleled their relative ER binding affinities (10-6 or 10-8-10-6 M, respectively). Combined treatment with the partial estrogen agonist, OH-tamoxifen, and E2 decreased E2-stimulated PTHrP secretion in MCF-7 cells to the levels seen with OH-tamoxifen treatment alone. These results suggest that transient estrogen- or tamoxifen-induced hypercalcemia in patients with breast carcinoma may be a PTHrP-mediated effect that is a marker of ER positivity.
UR - http://www.scopus.com/inward/record.url?scp=0032578786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032578786&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1998.9568
DO - 10.1006/bbrc.1998.9568
M3 - Article
C2 - 9790998
AN - SCOPUS:0032578786
VL - 251
SP - 849
EP - 854
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -