Comparative genomic hybridization of estrogen-induced ectopic uterine-like stem cell neoplasms in the hamster kidney: nonrandom chromosomal alterations.
Karyotype and comparative genomic hybridization (CGH) analyses were performed to identify nonrandom/consistent chromosomal alterations in solely estrogen (E)-induced primary ectopic uterine-like stem cell tumors in the kidney (EULTK) of the Syrian hamster, using a criterion of >/=20% frequency for nonrandom occurrence. Employing this criterion, EULTK karyotype analysis showed consistent gains in chromosomes 3, 6, 11, 14, 16, 20, and 21. Consistent trisomies were seen in all of these nonrandomly gained chromosomes. Only chromosomes 3 and 6 exhibited appreciable tetrasomies. Chromosome losses were observed consistently in chromosomes 7, 12, 17, and 19. Employing the same criterion, CGH analysis of primary EULTKs showed nonrandom amplified sequences at 1pa1-a4, 2cen-pter, 3pa1-a4, 6qb2-b4, 20qa1-a4, 21qa1-a2, Xqa3-qter and regional consistent losses at 1qc1-qter, 2qb1-c1, 3qa2-a7, 11qb5-qter, 15qa2-a5, 18qa2-a4, and 21pa. Moreover, 88% of the EULTKs examined exhibited amplification of the 6qb2-b4 region, where c-myc resides. The data presented lend credence to the supposition that chromosomal instability (CIN) is elicited by the upstream overexpression and subsequent amplification of c-myc by Es in multipotential interstitial uterine stem cells present in the kidney, thus leading to neoplastic development.
Hormonal Carcinogenesis Laboratory, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160-7417, USA.
Dan
D
Papa
Sara Antonia
SA
Li
Jonathan J
JJ
Li
D000782:Aneuploidy; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D002869:Chromosome Aberrations; D033481:Chromosomes, Mammalian / Q000235:genetics*; D006224:Cricetinae; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D017403:In Situ Hybridization; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008647:Mesocricetus; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D014594:Uterine Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism
D004967:Estrogens