V-K-ras transformation induces reversion to an earlier developmental form in adult rat adrenal cells.
The basis for specific changes in differentiation that accompany ras-oncogene-mediated transformation are not understood. When short-term cultures of fibroblast-like cells from adult rat adrenal glands were transformed with Kirsten murine sarcoma virus (KiMSV), the original stromal characteristics of the target cells (metachromatic extracellular matrix, high collagen production, collagen incorporation into pericellular matrix and a fibroblastic morphology and growth pattern) diminished. In contrast, parenchymal differentiation markers (neutral lipid, delta 5, 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase and epithelial morphology) were enhanced. These changes in differentiation were initiated concurrently with the over-expression of the transforming protein v-p21, but were unrelated to the levels of v-p21 expression. They were independent of the immortalizing component of transformation mediated by v-K-ras, because they did not take place in spontaneously immortalized lines derived from the same target cells, unless the lines were also transformed with KiMSV. In normal embryonic development, stromal and parenchymal adrenocortical cells arise by divergent differentiation pathways from a common, multipotential mesenchymal precursor. The transformation-induced modulation from a predominantly stromal to a more-parenchymal phenotype is thus reminiscent of reversion to a more primitive, bipotential developmental stage.
Department of Anatomy, University of British Columbia, Vancouver, Canada.
N
N
Auersperg
I A
IA
MacLaren
M J
MJ
Bissell
D015089:20-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000311:Adrenal Glands / Q000032:analysis / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis; D005109:Extracellular Matrix / Q000032:analysis / Q000201:enzymology; D011905:Genes, ras / Q000235:genetics*; D008055:Lipids / Q000032:analysis; D010641:Phenotype; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D014170:Transformation, Genetic
D008055:Lipids; D011518:Proto-Oncogene Proteins; D003094:Collagen; D015089:20-Hydroxysteroid Dehydrogenases; D016283:Proto-Oncogene Proteins p21(ras)