Stimulation of Growth by Both Androgen and Estrogen of the EMP-K1 Transplantable Tumor With Androgen and Estrogen Receptors From Human Extramammary Paget's Disease in Nude Mice

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Abstract
Background: Experimental approaches using transplantable human tumors in nude mice have greatly improved studies on their pathogenesis and treatment. Purpose: We studied the establishment of a transplantable tumor, EMP-K1, derived from extramammary Paget’s disease and the morphology and unique hormone dependence of this tumor. Methods: Tissue fragments from a metastatic skin tumor of an 80-year-old man with primary genital extramammary Paget‘s disease were implanted into male nude BALB/c mice. Tissue fragments of the established tumor were implanted into 50 castrated male 8-week-old nude mice, which were given injections of 100μg testosterone propionate (TP), 100 μg 5α-dihydrotestosterone (DHT), 10 μg diethylstilbestrol (DES), or 1, 10, or 100μg 17β-estradiol (E 2 ). All injections were administered intramuscularly once daily, starting from the day of transplantation. The established tumors were examined immunohisto-chemically and biochemically. Results: A transplantable tumor (EMP-K1) was established in the nude mouse. EMP-K1 tumor cells expressed antigens such as carcinoembryonic antigen and epithelial membrane antigen, cytokeratin, and c-erbB-2 protein and contained androgen, estrogen, and progesterone receptors. The growth of the EMP-K1 tumor was stimulated by TP, DHT, DES, and E 2 . Conclusions: These results suggest that both androgen and estrogen may stimulate the growth of the same tumor by both androgen receptor and estrogen receptor pathways. Implications: The EMP-K1 tumor is a useful tool for studies on the biology of extramammary Paget’s disease, and further studies using these tumors will provide useful information concerning proper hormone therapy. [J Natl Cancer Inst 84: 519–523, 1992]

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