Contrasting effects of 17 β-estradiol on the growth of human ovarian carcinoma cells in vitro and in vivo

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Abstract

A human ovarian adenocarcinoma cell line (PE04) has been established as a xenograft in nude mice. In vitro, this cell line is estrogen receptor (ER)-positive and its growth is stimulated by 17 β-estradiol at concentrations between 10−12 and 10−6 M. When xenografted, PE04 cells remain ER-positive and also possess progesterone receptors (PR); treatment with 17 β-estradiol reduces the concentration of ER and increases levels of PR. Growth of the xenograft is reduced in ovariectomized animals while implantation of estrogen pellets also results in growth inhibition. Similar treatment with estrogen does not inhibit the ER-negative HOX 60 ovarian xenograft, and stimulates growth of the ER-positive ZR-75-1 breast carcinoma xenograft. Serum measurements of 17 β-estradiol confirm that ovariectomy reduces the level of 17 β-estradiol while implantation of estrogen pellets results in raised levels of the hormone. Tamoxifen inhibits growth of the PE04 xenograft but not that of the HOX 60 xenograft, consistent with ER status. These results indicate that ER-positive PE04 ovarian cancer cells are sensitive to 17 β-estradiol in vivo but that the response may be of a different type from the in vitro response. This lends further support to the concept that ovarian cancer may be hormone-sensitive and potentially responsive to endocrine therapy.

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