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Effect of Retinoic Acid on Proliferation of Estrogen-responsive Transformed Murine Leydig Cells in Serum-free Culture

Takahisa Hirose, Masafumi Koga, Haruhiko Kouhara, Susumu Kishimoto, Keishi Matsumoto and Bunzo Sato
Takahisa Hirose
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Masafumi Koga
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Haruhiko Kouhara
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Susumu Kishimoto
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Keishi Matsumoto
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Bunzo Sato
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DOI:  Published August 1990
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Abstract

B-1 F cells, one of the sublines established from mouse Leydig cell tumor, have been found to be maintained as an estrogen-responsive cell line under the serum-free culture conditions. Reported results that retinoids have action mechanisms similar to those of estrogen prompted us to examine the effect of retinoids on the proliferation of B-1 F cells.

Stimulation of B-1 F cell growth by retinoic acid in a dose-dependent manner was observed, whereas retinoic acid did not promote but inhibited the proliferation of MCF-7 cells (estrogen- and retinoic acid receptor-positive human breast cancer cells). To elucidate the mechanism of retinoic acid-dependent cell growth, simultaneous treatment with retinoic acid and estradiol was carried out. The result did not show the additive effect on B-1 F cell growth. Hydroxytamoxifen, a potent antiestrogen, inhibited not only estradiol-dependent but also retinoic acid-dependent cell growth. However, retinoic acid failed to be associated with estrogen receptor, suggesting that retinoic acid induced enhancement of B-1 cell growth through its interaction with retinoic acid receptor. Northern blot analyses of polyadenylated RNA with complementary DNA probes for human retinoic acid receptor α, β, and γ revealed the presence of transcripts encoded by retinoic acid receptor α gene in B-1 F cells.

These results would suggest that enhancement of the B-1 F cell growth is mediated through interaction of retinoic acid with retinoic acid receptor α. This stimulatory activity is inhibited by estrogen receptor complexed with hydroxytamoxifen.

Footnotes

  • ↵1 Supported by grants from the Ministry of Education, Tokyo; Hisamitsu Cancer Research Fund; and Hirai Cancer Research Fund.

  • ↵2 To whom requests for reprints should be addressed.

  • Received August 30, 1989.
  • Revision received May 1, 1990.
  • ©1990 American Association for Cancer Research.
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August 1990
Volume 50, Issue 16
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Effect of Retinoic Acid on Proliferation of Estrogen-responsive Transformed Murine Leydig Cells in Serum-free Culture
Takahisa Hirose, Masafumi Koga, Haruhiko Kouhara, Susumu Kishimoto, Keishi Matsumoto and Bunzo Sato
Cancer Res August 15 1990 (50) (16) 5060-5064;

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Effect of Retinoic Acid on Proliferation of Estrogen-responsive Transformed Murine Leydig Cells in Serum-free Culture
Takahisa Hirose, Masafumi Koga, Haruhiko Kouhara, Susumu Kishimoto, Keishi Matsumoto and Bunzo Sato
Cancer Res August 15 1990 (50) (16) 5060-5064;
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Cancer Research Online ISSN: 1538-7445
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