Sertoli Cell Differentiation on Basement Membrane is Mediated by the c-fos Protooncogene

When Sertoli cells of the seminiferous epithelium in the testis were cultured on Matrigel (a reconstituted basement membrane), laminin, or one of the biologically active laminin-derived peptides (YIGSR, SIKVAV, or RGD), they exhibited dramatic changes in morphology accompanied by changes in protein...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-07, Vol.91 (15), p.7027-7031
Main Authors: Papadopoulos, Vassilios, Dym, Martin
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Basement membrane
Basement Membrane - metabolism
Cell culture techniques
Cell Differentiation
Cells
Cells, Cultured
Cellular biology
Cellular differentiation
Cultured cells
DNA
Epithelial cells
Extracellular matrix
Genes
Genes, fos
Male
Messenger RNA
Molecular Sequence Data
Proto-Oncogene Proteins c-fos - genetics
Rats
Sertoli cells
Sertoli Cells - cytology
Transcription factors
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Summary:When Sertoli cells of the seminiferous epithelium in the testis were cultured on Matrigel (a reconstituted basement membrane), laminin, or one of the biologically active laminin-derived peptides (YIGSR, SIKVAV, or RGD), they exhibited dramatic changes in morphology accompanied by changes in protein secretion and gene expression, including a rapidly induced stimulation of c-fos mRNA. To examine the role of c-fos in Sertoli cell attachment, spreading, and differentiation on extracellular matrix, we constructed sense and antisense c-fos phosphorothioate oligodeoxynucleotides (ODNs). Sertoli cells, in small clumps of 10-20 cells, cultured on Matrigel or laminin in the presence of ODNs antisense to c-fos (30 μ g/ml) did not spread for the first 10-20 hr. After that time, normal spreading occurred, probably as a result of ODN degradation. Cells cultured in medium supplemented with ODNs sense to c-fos (30 μ g/ml), or without ODNs, spread within 30 min to 1 hr, and after 12 hr a monolayer was established. Furthermore, incubation of Sertoli cells with ODNs antisense to c-fos resulted in a significant reduction of c-fos protein levels, whereas treatment with ODNs sense to c-fos barely affected c-fos protein expression. These data indicate that c-fos may mediate the events involved in Sertoli cell attachment and spreading upon contact of the cells with extracellular matrix.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.15.7027