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

  • Abraham Amsterdam
  • Lea Eisenbach
  • Byung Sun Suh
  • Debora Plehn-Dujowich
  • Iris Keren Tal
  • Ada Dantes
Part of the NATO ASI Series book series (NSSA, volume 220)


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.


Granulosa Cell Granulosa Cell Tumor Steroidogenic Enzyme Preantral Follicle Progesterone Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Abraham Amsterdam
    • 1
  • Lea Eisenbach
    • 2
  • Byung Sun Suh
    • 1
  • Debora Plehn-Dujowich
    • 1
  • Iris Keren Tal
    • 1
  • Ada Dantes
    • 1
  1. 1.Department of Hormone ResearchThe Weizmann Institute of ScienceRehovotIsrael
  2. 2.Department of Cell BiologyThe Weizmann Institute of ScienceRehovotIsrael

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