Use of representational difference analysis for the identification of mdm2 oncogene amplification in diethylstilbestrol-induced murine uterine adenocarcinomas.
Exposure in utero to the synthetic estrogen diethylstilbestrol (DES) is associated with the subsequent development of reproductive-tract malignancies in female offspring. To search for the genetic targets of DES, representational difference analysis was used to compare genomic DNA from DES-associated mouse uterine adenocarcinoma cells with genomic DNA from normal CD-1 mouse tissue. Several difference clones were obtained, all of which recognized rearranged and amplified sequences in tumor compared with normal DNA. One of these difference fragments mapped to a region of mouse chromosome 10 that includes the mdm2 oncogene. Amplification and overexpression of mdm2 was found in all three early-passage cell lines established from independent DES-associated cancers. These findings demonstrate the potential power of representational difference analysis in cancer research and suggest a genetic mechanism for DES-induced carcinogenesis.
Risinger
J I
JI
Gynecologic Pathobiology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.
Terry
L A
LA
Boyd
J
J
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D018244:Chromosomes, Artificial, Yeast; D003001:Cloning, Molecular / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics*; D004054:Diethylstilbestrol / Q000494:pharmacology*; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D051379:Mice; D009857:Oncogenes; D016133:Polymerase Chain Reaction / Q000379:methods*; D014594:Uterine Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D004054:Diethylstilbestrol