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Possible Role for Ha-ras Expression in Inducible Steroidogenesis in Immortalized Granulosa Cell Lines

  • Chapter
The Superfamily of ras-Related Genes

Part of the book series: NATO ASI Series ((NSSA,volume 220))

Abstract

Primary granulosa cells cotransfected with SV40 DNA and the Ha-ras oncogene can be induced to produce progestins (progesterone and 20α-dihydroprogesterone) when incubated with 8-Br-cyclic AMP and substances elevating intracellular cyclic AMP (cAMP) such as forskolin, choleratoxin and the Bordetella pertussis invasive adenylate cyclase (BPAC). In contrast, cells transfected with SV40 DNA alone show only traces of steroidogenic activity under similar stimulation. The steroidogenic capacity of the cotransfected lines was correlated with the epithelioid appearance of the cells and low expression of actin and actin binding proteins in these cells. Expression of isoforms 2 and 3 of tropomyosins which possess high affinity for actin filaments was extremely low in these cells compared to cells transfected with SV40 DNA alone. Expression of p21 in cotransfected individual lines was correlated to the steroidogenic capacity. Primary granulosa cells and luteinized cells also express modestly but significantly p21 precipitable by monoclonal antibodies against the proto/mutated oncogene product. The cotransfected cells were highly tumorigenic when injected to nude mice but pretreatment of the cells with BPAC, which resulted in prolonged intracellular accumulation of cAMP, prevented metastatic spread of the tumor cells. Therefore, high levels of intracellular cAMP may arrest proliferation of the transformed cells both in vivo and in vitro. It is suggested that the expression of the Ha-ras oncogene may be involved in inducible steroidogenesis in immortalized granulosa cell lines, while the product of the protooncogene may be implicated in this process in normal cells.

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Authors and Affiliations

  1. Department of Hormone Research, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Abraham Amsterdam, Byung Sun Suh, Debora Plehn-Dujowich, Iris Keren Tal & Ada Dantes

  2. Department of Cell Biology, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Lea Eisenbach

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  1. Abraham Amsterdam
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  2. Lea Eisenbach
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  1. National Hellenic Research Foundation, Athens, Greece

    Demetrios A. Spandidos

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© 1991 Plenum Press, New York

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Amsterdam, A., Eisenbach, L., Suh, B.S., Plehn-Dujowich, D., Tal, I.K., Dantes, A. (1991). Possible Role for Ha-ras Expression in Inducible Steroidogenesis in Immortalized Granulosa Cell Lines. In: Spandidos, D.A. (eds) The Superfamily of ras-Related Genes. NATO ASI Series, vol 220. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-6018-6_25

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  • DOI: https://doi.org/10.1007/978-1-4684-6018-6_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-6020-9

  • Online ISBN: 978-1-4684-6018-6

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