Altered expression of proto-oncogenes in human lymphoid cells immortalized by transfection with extrachromosomal DNA of mouse L cells.
Human lymphocytes were induced to proliferate continuously in vitro by transfection with extrachromosomal DNA from mouse L929 cytoplasts. The immortalized cells contain 2- to 5-fold increased mRNA levels of only 3 (c-Ha-ras-1, c-Ki-ras, c-myc) out of 18 proto-oncogenes tested compared to quiescent lymphocytes. Furthermore, the immortalized cells contain decreased amounts of c-fos mRNA, 2- to 20-fold decreased amounts of lck and c-fgr mRNA and 10-fold increased levels of JD15 mRNA compared to primary lymphocytes. The immortalised cells do not harbor amplified copies or any major rearrangement of these genes. No additional copy of these genes transferred from the mouse genome could be detected in the immortalized human cell lines. Thus, the changes in the level of these proto-oncogene transcripts in the lymphoid cells are likely to be induced by the immortalizing DNA from L929 cytoplasts and appear to be associated with continuous proliferation of these cells. Since the immortalized cell lines do not form colonies in soft agar medium and do not induce tumors in nude mice, we suggest that the altered expression of these proto-oncogenes may be due to the transition from quiescent to continuous proliferation in vitro ("immortalization"), but does not correlate with a tumorigenic phenotype of the cells.
Abken
H
H
Abteilung Molekulargenetik, Universität Bonn, Fed. Rep. Germany.
Bützler
C
C
Willecke
K
K
D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007739:L Cells; D008214:Lymphocytes / Q000378:metabolism*; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger