Biological and biochemical characterization of estrogen-dependent mouse Leydig cell tumors.
Leydig cell tumors formed in BALB/c mice were found to be able to be transplanted subcutaneously in the same strain. One of the sublines, called T 22137, showed growth inhibition in response to estrogenization of host mice. The other subline (T 124958-O), which was originally classified as an estrogen-independent line, was observed to contain the low-affinity estradiol binding component in the cytosol fraction. At a later stage of transplantation, however, the growth of this subline was modestly but significantly enhanced by estrogenic stimuli. This alteration was accompanied by appearance of an estrogen receptor-like molecule which was associated with chromatin even in the absence of estrogen stimuli. In the presence of estrogen selection pressure, a new tumor line, designated as T 124958-R, was established, which showed marked estrogen-dependent growth. T 124958-R was found to contain the cytosolic estrogen receptor. The additional difference was that the annulate lamellae were identified only in T 124958-R, but not in T 124958, by electron microscopic studies. The estrogen dependency of T 124958-R was further substantiated by demonstration of an estrogen secretory protein as well as the estrogen-enhanced formation of 5 alpha-steroids. T 22137 showed growth inhibition in tamoxifen-treated mice. The growth of T 124958-R was enhanced by the administration of tamoxifen to mice. This tamoxifen-induced tumor growth was further stimulated by the simultaneous administration of estrogen. These observations would suggest that mouse Leydig cell tumor systems provide us with a valuable model to investigate the influence of estrogen as well as antiestrogen on malignant cells.
Third Department of Internal Medicine, Osaka University Hospital, Japan.
B
B
Sato
Y
Y
Miyashita
Y
Y
Nishizawa
K
K
Noma
S
S
Kishimoto
H
H
Mori
K
K
Matsumoto
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens; D007984:Leydig Cell Tumor / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000648:ultrastructure; D011959:Receptors, Estradiol / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004967:Estrogens; D009363:Neoplasm Proteins; D011959:Receptors, Estradiol; D013629:Tamoxifen; D004958:Estradiol; D004054:Diethylstilbestrol; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase