The competence of transformed keratinocytes to differentiate is accompanied by amplification of the LDL- and EGF-receptor genes but not of the insulin receptor gene.
The possible relationship between cell surface receptor numbers, receptor gene expression for low density lipoprotein (LDL), insulin and epidermal growth factor (EGF), and differentiation capacity has been studied in normal and SV40 transformed (SVK14) keratinocytes, various squamous carcinoma cell (SCC) lines and A431 cells. Our recent studies demonstrated that an inverse relationship exists between LDL- and EGF-receptor binding and the ability to differentiate of both normal and transformed keratinocytes. In the present study cloned LDL- and EGF-receptor complementary DNAs were used as probes to identify both LDL and EGF receptor gene fragments on genomic DNA blots. The extent of hybridisation was found to be increased to the highest extent in A431 cells and decreased in other cells in the following order SCC-4 greater than SCC-15. In SCC-12F2, SVK14 and normal keratinocytes no increase has been observed. The increased hybridisation of LDL- and EGF-receptors in A431, SCC-4 and SCC-15 cells was found to be due to gene amplification and not to aneuploidy. In contrast to the LDL- and EGF-receptor binding, no correlation has been found between insulin receptor binding and ability of cells to differentiate. Furthermore, no amplification of insulin receptor gene has been observed in any of the cells under study.
te Pas
M F
MF
Department of Dermatology, University Hospital Leiden, The Netherlands.
Boonstra
J
J
Havekes
L
L
Hesseling
S C
SC
Ponec
M
M
D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009693:Nucleic Acid Hybridization; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000166:cytology*
D011973:Receptors, LDL; D004247:DNA; D066246:ErbB Receptors; D011972:Receptor, Insulin