Susceptibility to ras oncogene transformation is coregulated with signal transduction through growth factor receptors.
The human teratocarcinoma cell line PA-1 was derived from culturing ascites fluid cells from a patient with an ovarian germ line tumor. We previously described a non-neoplastic variant cloned from the PA-1 human teratocarcinoma cell line, clone 6, which at passage 40 was resistant to transformation by activated ras oncogenes. However, these cells could be transformed by a plasmid containing both myc and ras. Another PA-1 cell variant, clone 1, isolated at passage 63 and used 50 passages later becomes tumorigenic in nude mice after transfection with an activated ras oncogene (Tainsky et al., Anticancer Res., 8, 899-914, 1988). We report here that the progression from ras resistance to ras susceptibility occurs in both clone 1 and clone 6 cells during 25 passages in culture. In the presence of epidermal growth factor, transforming growth factor-alpha, and basic fibroblast growth factor, the ras-transformable cells exhibit anchorage independent growth, whereas the ras-resistant cells can not be growth stimulated by these growth factors. Similarly, ornithine decarboxylase (ODC) activity was inducible in ras susceptible and ras transformed cells by these growth factors, but not in the ras resistant cells. These differences are not due to the level and activity of epidermal growth factor receptor or to the level of expression of 25 proto-oncogenes.
Chiao
P J
PJ
Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Kannan
P
P
Yim
S O
SO
Krizman
D B
DB
Wu
T A
TA
Gallick
G E
GE
Tainsky
M A
MA
D015152:Blotting, Northern; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D011905:Genes, ras; D006801:Humans; D015151:Immunoblotting; D009857:Oncogenes; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor; D015398:Signal Transduction; D013724:Teratoma
D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D009955:Ornithine Decarboxylase