NIH3T3 fibroblasts transformed by the dbl oncogene show altered expression of bradykinin receptors: effect on inositol lipid turnover.
We have examined polyphosphoinositide turnover in mouse fibroblasts (NIH3T3) transformed by the dbl oncogene as compared to normal cells. The dbl-transformed fibroblasts did not show alterations of the basal level of inositol polyphosphates, polyphosphoinositides, diacylglycerol or phosphatidic acid. This indicates that the activity of C-type phospholipases, inositol lipid kinases and diacylglycerol kinase is not altered in dbl-induced transformation. However, dbl-transformed NIH3T3 cells exhibited increased inositol lipid turnover in response to bradykinin. Further analysis revealed significantly higher number of bradykinin receptors in dbl transfectants as compared to control NIH3T3. When several clonally-derived dbl NIH3T3 transfectants were analyzed, we observed a large variation of their bradykinin receptor number. Cell lines exhibiting increased bradykinin binding, however, failed to show augmented mitogenic response to the peptide agonist. Among other oncogenes, only ras showed a similar effect. We conclude that increased bradykinin receptor number is a phenomenon observed with several cell lines transformed by different oncogenes, and it does not correlate with either enhanced mitogenic responsiveness of transformed cells to the peptide, or with the presence of a specific oncogene in the transformant.
Ruggiero
M
M
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Srivastava
S K
SK
Fleming
T P
TP
Ron
D
D
Eva
A
A
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D005347:Fibroblasts / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D009857:Oncogenes; D010716:Phosphatidylinositols / Q000378:metabolism*; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000187:drug effects; D012191:Retroviridae Proteins / Q000235:genetics / Q000502:physiology*; D015682:Retroviridae Proteins, Oncogenic
D020662:Guanine Nucleotide Exchange Factors; C512843:Mcf2 protein, mouse; D010716:Phosphatidylinositols; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; D001920:Bradykinin