Changes in the expression and binding properties of the estrogen receptor in MCF-7 breast cancer cells during growth inhibition by tamoxifen and cisplatin

Citation
Am. Otto et al., Changes in the expression and binding properties of the estrogen receptor in MCF-7 breast cancer cells during growth inhibition by tamoxifen and cisplatin, CANC CHEMOT, 48(4), 2001, pp. 305-311
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER CHEMOTHERAPY AND PHARMACOLOGY
ISSN journal
0344-5704 → ACNP
Volume
48
Issue
4
Year of publication
2001
Pages
305 - 311
Database
ISI
SICI code
0344-5704(200110)48:4<305:CITEAB>2.0.ZU;2-I
Abstract
Most mammary carcinomas contain estrogen receptors (ER), which are an impor tant factor in diagnosis and prognosis, and in deciding on the type of ther apy. ER-positive tumors are most commonly treated with the antiestrogen tam oxifen or with a combination of chemotherapeutic drugs. An important aspect for further treatment and anticipating possible side effects is the fate o f the ER during the course of therapy. To study the effect of drug-induced growth inhibition on ER expression and binding properties. human breast can cer MCF-7 cells were treated with tamoxifen and cisplatin., and also estrad iol (E-2) for 5 days. Following this incubation, intact cells were incubate d with [H-3]E-2 to determine the dissociation constant (KD) and maximal num ber of binding sites (B-max) of the ER. The amount of ER protein per cell w as quantified using anti-ER antibodies. For analysis of ER mRNA, total cell ular RNA was subjected to Northern blotting. The 5-day treatment with E, re duced B-max and the amount of ER protein by about 70%, while the cellular l evel of ER mRNA was reduced by 40%. Treatment with E, did not affect the su bsequent growth inhibitory response to tamoxifen or cisplatin. In contrast, tamoxifen reduced the capacity for E, binding, it caused about a 30-fold i ncrease in the KD value. At the same time, B-max, and ER protein content we re increased (about 3.5- and 2-fold. respectively). but the cellular level of ER mRNA was again reduced by 40%. The growth of tamoxifen-treated cells remained sensitive to subsequent treatment with estradiol. tamoxifen or cis platin. Treatment of MCF-7 cells with cisplatin likewise reduced E-2 bindin g due to a 20-fold increase in KD value. In this case, both Bma, and the am ount of ER protein were decreased when calculated per milligram of protein, but were increased on a cellular basis due to an increase in cell size. Th e ER mRNA content was not altered in cisplatin-treated cells. Growth of the se cells also remained sensitive to tamoxifen and cisplatin. In conclusion, drug-induced changes in ER expression and binding capacity do not necessar ily indicate a loss of sensitivity of breast cancer cells to a subsequent c hemotherapeutic treatment.