TY - JOUR
T1 - Understanding the biologic mechanisms responsible for breast-cancer progression during tamoxifen or fulvestrant treatment
AU - Hardin, Chelsea
AU - Pommier, Rodney
AU - Lefleur, Brett
AU - Jackson, Terisa
AU - Toth-Fejel, Su Ellen
PY - 2004/10
Y1 - 2004/10
N2 - Dehydroepiandosterone sulfate (DHEAS) causes breast-cancer proliferation, even during tamoxifen or fulvestrant blockade. The purpose of this study was to determine possible mechanisms for this treatment failure. T-47D cells (estrogen receptor [ER] and progesterone receptor [PR] positive) were treated with fulvestrant (10 mol/L), tamoxifen (10 mmol/L or 0.0001 nmol/L), or vehicle and stimulated with DHEAS. Gene expression of ER, PR, insulin-like growth factor (IGF)-1 and -2, and insulin-like growth-factor binding protein (IGFBP)-1 through -4 was determined. ER and PR gene expression decreased by 1.3- and 4-fold with fulvestrant and DHEAS. ER expression decreased by 2.7-fold with 0.0001 nmol/L tamoxifen and DHEAS. ER and PR expression were unchanged by 10 nmol/L tamoxifen. IGF-1 and IGF-2 were not expressed. IGFBP-2 and -4 expression decreased by 1.9- and 1.6-fold after DHEAS stimulus, although this was not statistically significant. DHEAS exposure, even in the presence of tamoxifen and fulvestrant, induces changes in ER and PR gene expression that may be partially responsible for breast cancer progression.
AB - Dehydroepiandosterone sulfate (DHEAS) causes breast-cancer proliferation, even during tamoxifen or fulvestrant blockade. The purpose of this study was to determine possible mechanisms for this treatment failure. T-47D cells (estrogen receptor [ER] and progesterone receptor [PR] positive) were treated with fulvestrant (10 mol/L), tamoxifen (10 mmol/L or 0.0001 nmol/L), or vehicle and stimulated with DHEAS. Gene expression of ER, PR, insulin-like growth factor (IGF)-1 and -2, and insulin-like growth-factor binding protein (IGFBP)-1 through -4 was determined. ER and PR gene expression decreased by 1.3- and 4-fold with fulvestrant and DHEAS. ER expression decreased by 2.7-fold with 0.0001 nmol/L tamoxifen and DHEAS. ER and PR expression were unchanged by 10 nmol/L tamoxifen. IGF-1 and IGF-2 were not expressed. IGFBP-2 and -4 expression decreased by 1.9- and 1.6-fold after DHEAS stimulus, although this was not statistically significant. DHEAS exposure, even in the presence of tamoxifen and fulvestrant, induces changes in ER and PR gene expression that may be partially responsible for breast cancer progression.
KW - Breast cancer
KW - Dehydroepiandosterone sulfate
KW - Estrogen receptor
KW - Fulvestrant
KW - Insulin-like growth factor
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=4944259832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4944259832&partnerID=8YFLogxK
U2 - 10.1016/j.amjsurg.2004.06.017
DO - 10.1016/j.amjsurg.2004.06.017
M3 - Article
C2 - 15474441
AN - SCOPUS:4944259832
SN - 0002-9610
VL - 188
SP - 426
EP - 428
JO - American journal of surgery
JF - American journal of surgery
IS - 4 SPEC. ISS.
ER -