In order to better understand the structural requirements for effective high affinity binding of estrogens and antiestrogens by the human estrogen receptor (ER), a comparative study was undertaken in which we examined: 1) native ER from the MCF-7 ER-positive human breast cancer cell line; 2) full length ER expressed in yeast; 3) the ER hormone binding domain (amino acid residues 302-595) expressed in yeast; 4) a bacterially expressed protein A fusion product encoding a truncated ER (amino acid residues 240-595); and 5) a synthetic peptide encompassing amino acids 510-551 of the ER.
Since the poor prognosis associated with HER2 amplified breast cancers might be explained by a mechanistic association between p185HER2 overexpression and therapeutic resistance, we assessed the chemo-endocrine sensitivity of estrogen receptor (ER) containing MCF-7 breast cancer cells transfected with full-length HER2 cDNA.
The increasing evidence for the association of heat-shock proteins with steroid receptors suggests that AJ1 may play an important role in the control of estrogen-receptor transcriptional activity in breast cancers.
The glutathione S-transferase pi gene (GST pi) is highly expressed in estrogen receptor negative (ER-) but not expressed in ER+ human breast cancer cell lines.
We found that some progestins used in OC were able to stimulate the growth of estrogen receptor-positive (ER+) MCF-7 and T47DA18 human breast cancer cells but not ER- MDA-MB-231, BT-20, and T47DC4 human breast cancer cells.
It is fairly well accepted that the presence of estrogen receptor (ER) and progesterone receptor (PgR) identifies breast cancer patients with a lower risk of relapse and better overall survival.
Data from these cell lines suggest that human breast cancer progression results first in the loss of ER, and subsequently in VIM acquisition, the latter being associated with increased metastatic potential through enhanced invasiveness.
Previous reports indicate that the two-allele ER PvuII polymorphism could be associated with ER expression in breast cancer (Hill et al., Cancer Res., 49: 145-148, 1989) as well as with patient age at time of tumor diagnosis (Parl et al., Breast Cancer Res.Treat., 14: 57-64, 1989).
Additionally, the methylation pattern of the estrogen-receptor gene (6q24-27), whose protein product is increased in numerous breast cancers, also did not change.
Previously, we demonstrated that the progestin components (19-nortestosterone derivatives) in oral contraceptives are able to stimulate human breast cancer cell proliferation via an estrogen receptor (ER)-mediated mechanism.
Three 125I-iodinated estrogen derivatives; 16 alpha-[125I]iodo-11 beta-methoxy-17 beta-estradiol ([125I]IME2), E-17 alpha-[125I]iodovinylestradiol ([125I]IVE2) and E-17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol ([125I]MIVE2) were synthesized with high specific activities and their binding characteristics and biological effects were analyzed in vitro using the estrogen-receptor-positive human breast cancer cell line MCF-7.
Moreover, the same estradiol effect was observed in the ZR75-1 cell line and in MDA-MB231 estrogen-resistant breast cancer cells stably transfected with the estrogen receptor.
Because that study evaluated only women with estrogen receptor positive (ER+) breast cancer, it was unknown whether the observed correlation was restricted to the cancer group or was independent of breast cancer.
These variants were identified using the polymerase chain reaction to perform directed cloning of ER cDNAs synthesized from polyadenylated RNA extracted from the human breast cancer cell line T47D.