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Use of representational difference analysis for the identification of mdm2 oncogene amplification in diethylstilbestrol‐induced murine uterine adenocarcinomas
Author(s) -
Risinger John I.,
Terry Lori A.,
Boyd Jeff
Publication year - 1994
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940110104
Subject(s) - biology , diethylstilbestrol , oncogene , mdm2 , identification (biology) , cancer research , computational biology , microbiology and biotechnology , genetics , medicine , cancer , estrogen , cell culture , cell cycle , botany
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. ©1994 Wiley‐Liss, Inc.