Integration of proviral sequences, but not at the common integration sites of the FGF8 locus, in an androgen-dependent mouse mammary Shionogi carcinoma.
A retroviral insertional mutation, especially by mouse mammary tumor virus (MMTV), is a major cause of murine mammary tumorigenesis. Prompted by our previous finding that FGF8, an insertionally activated cellular oncogene, is highly expressed in androgen-dependent mouse mammary Shionogi carcinoma cells, we here investigated retroviral integration adjacent to the fgf8 locus in Shionogi carcinoma. In the genomic Southern blots for fgf8 and its 5'-upstream gene npm3, the hybridized fragments were identical to the host DD/Sio mice, the original Shionogi carcinoma 115 tumor, and a pair of cultured Shionogi carcinoma cell lines of SC-3 and SC-4, suggesting that no retroviral integration occurred around either loci. The genomic cloning for the fgf8 locus from SC-3 cells also confirmed no MMTV integration. In addition, npm3, which is usually coactivated with fgf8 by MMTV insertion,was not up-regulated by androgens in SC-3 cells. All these findings led us to conclude that no retroviral insertion was present at the common integration sites adjacent to the fgf8 locus in Shionogi carcinoma although we demonstrated in this study that multiple proviral sequences of MMTV, Moloney murine sarcoma virus and FBJ-murine sarcoma virus are integrated into SC-3 cells in association with their distinct promoter activity in SC-3 cells.
Kuriki
K
K
Department of Pathology, Jichi Medical School, Kawachi, Tochigi, Japan.
Kamiakito
T
T
Yoshida
H
H
Saito
K
K
Fukayama
M
M
Tanaka
A
A
D000818:Animals; D051379:Mice; D000595:Amino Acid Sequence; D000728:Androgens / Q000494:pharmacology; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000235:genetics / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D056489:Nucleoplasmins; D010750:Phosphoproteins / Q000235:genetics; D015183:Restriction Mapping; D012192:Retroviridae Infections / Q000139:chemically induced / Q000235:genetics / Q000821:virology; D016415:Sequence Alignment; D020079:Terminal Repeat Sequences / Q000235:genetics; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000139:chemically induced / Q000235:genetics / Q000821:virology; D016662:Virus Integration / Q000235:genetics
D000728:Androgens; C496457:Fgf8 protein, mouse; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D009687:Nuclear Proteins; D056489:Nucleoplasmins; D010750:Phosphoproteins; C533552:Npm2 protein, mouse