The effect and mechanisms of
17 beta-estradiol (E2) on
breast cancer cells were studied in vivo and in vitro, using 5 human
breast carcinomas serially transplanted into nude mice. These
carcinoma strains consisted of 4
estrogen receptor (ER) positive
tumors and 1 ER negative
tumor. Mice bearing these
tumors were treated with an
intramuscular injection of E2 at a dosage of 50 mg/kg and the
tumor doubling time (Td) was calculated in days. The
tumor growth was significantly stimulated by E2 in 3 out of the 4 ER positive
tumors, the Td of the E2 treated groups being 17.6 days for MCF-7 (control: -17.8 days), 12.8 days for R-27 (control: -12.5 days approximately 14.5 days) and 10.4 days for Br-10 (control: 14.5 days), however, in the
T-61 tumor, the growth was inhibited by E2 in a dose dependent manner. In the case of the ER-negative MX-1
tumor, the
tumor cell growth was not affected by E2. Discrepancies between the effects of E2 on ER-positive
tumors were further analyzed by examining the
steroid hormone receptor status and conducting in vitro growth studies. In vitro clonogenic cell assay reproduced the antitumor activity of E2, indicating that E2 directly inhibits part of the cell growth of
T-61 tumors. The above results suggest that this experimental system provides a useful tool for analyzing the mechanism of
estrogen in
breast cancer and that the clonogenic assay using ER positive specimens can help to identify breast
cancers sensitive to
estrogen therapy.