Activation of c-mos oncogene by integration of an endogenous long terminal repeat element during transfection of genomic DNA from mouse skin tumor cells.
An activated c-mos oncogene was identified in a transformed clone of golden hamster embryo cells transfected with DNA extracted from cells cultured from a UV-induced mouse skin tumor. Southern blot hybridization with a v-mos oncogene probe showed that the mos oncogene was amplified in the primary and secondary transformed cells but not in the original tumor cells. Expression of the mos oncogene was very high in the primary and secondary transformants, but mos mRNA was undetectable in the original tumor cells. A genomic DNA fragment containing the activated mos oncogene was cloned and sequenced. The upstream mouse sequence of the mos oncogene, which functions as the transcription terminator, was lost and replaced by a mouse endogenous long terminal repeat (LTR) element that provides the promoter sequence, resulting in high expression of the gene. The rearrangement apparently occurred during transfection, since the polymerase chain reaction (PCR) product encompassing the junction region was present in the primary and secondary transformants but not in the original tumor cells. The LTR element is likely to have been amplified during the skin tumor development caused by UV irradiation. Southern blot hybridization showed that the copy number of LTR in the tumor cells was significantly higher than that in normal skin cells. The amplification of the LTR in the cells may have increased the chance of recombination between the LTR and c-mos gene during the DNA transfection.
Wang
S
S
Department of Experimental Radiology, Faculty of Medicine, Kyoto University, Japan.
Nishigori
C
C
Miyakoshi
J
J
Tsukada
T
T
Shung
B
B
Yagi
T
T
Takebe
H
H
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D016258:Genes, mos; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D017384:Sequence Deletion; D012878:Skin Neoplasms / Q000235:genetics*; D014162:Transfection
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm