Estrogen receptor expression and estrogen receptor-independent cytotoxic effects of tamoxifen on malignant rhabdoid tumor cells in vitro.
Recent studies have shown that the antiestrogen tamoxifen (TAM) can be used in the treatment of malignant neoplasms other than breast cancer. In the present study, we investigated the expression of estrogen receptor (ER) in six malignant rhabdoid tumor (MRT) cell lines. Alterations in MRT cell growth in response to estrogen or antiestrogens (4-hydroxytamoxifen (4-OHT), TAM, and ICI 182 780) were also investigated. RT-PCR and western blotting showed that ER-alpha was expressed in three of the six MRT cell lines. While 17-beta-estradiol (E2) did not significantly alter MRT cell line proliferation, the hydroxylated tamoxifen metabolite 4-OHT significantly inhibited the growth of all 6 MRT cell lines. However, the steroidal antiestrogen ICI 182 780 did not alter the proliferation of any of the MRT cell lines. 4-OHT induced apoptosis in both ER-alpha-negative and ER-alpha-positive MRT cell lines, as assessed by nuclear morphology and DNA fragmentation. Neither growth inhibition nor induction of apoptosis due to 4-OHT was blocked by the addition of excess E2. Our data suggested that 4-OHT induced cytotoxic effects against MRT cells, and that these effects were independent of ER expression.
Koshida
Shigeki
S
Department of Pediatrics, Shiga University of Medical Science, Seta, Ohtsu, Shiga 520-2192, Japan.
Narita
Tsutomu
T
Kato
Hirofumi
H
Yoshida
Shinobu
S
Taga
Takashi
T
Ohta
Shigeru
S
Takeuchi
Yoshihiro
Y
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011960:Receptors, Estrogen / Q000032:analysis* / Q000502:physiology; D018335:Rhabdoid Tumor / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol