RESUMO
Mice carrying the MMTV-cmyc transgene develop mammary tumors at 9 to 12 months of age. Little is known about karyotypic changes in this model of human breast cancer. We have developed and applied molecular cytogenetic techniques to study chromosomal aberrations that occur in these tumors, namely, comparative genomic hybridization and spectral karyotyping. Cell lines from eight tumors were established and analyzed, four of which carried a heterozygous p53 mutation. All of the tumor cell lines revealed increases in ploidy and/or multiple numerical and structural chromosomal aberrations. No consistent differences were observed between cmyc/p53+/+ and cmyc/p53+/- tumors, suggesting that cmyc induces karyotype instability independent of p53 status. Loss of whole chromosome (Chr) 4 was detected in five of the eight tumors. Parts of Chr 4 are syntenic to human 1p31-p36, a region that is also deleted in human breast carcinomas. Four tumors carried translocations involving the distal portion of Chr 11 (syntenic to human chromosome arm 17q), including two translocations T(X;11), with cytogenetically identical breakpoints. We compare the pattern of chromosomal aberrations with human breast cancers, find similarities in several syntenic regions, and discuss the potential of an interspecies cytogenetic map of chromosomal gains and losses.
Assuntos
Aberrações Cromossômicas/genética , Genes myc/genética , Neoplasias Mamárias Experimentais/genética , Vírus do Tumor Mamário do Camundongo/genética , Infecções por Retroviridae/genética , Infecções Tumorais por Vírus/genética , Animais , Neoplasias da Mama/genética , Deleção Cromossômica , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 8/genética , Modelos Animais de Doenças , Amplificação de Genes/genética , Humanos , Cariotipagem , Camundongos , Camundongos Transgênicos , Hibridização de Ácido Nucleico/métodos , Ploidias , Células Tumorais CultivadasRESUMO
There is a family of genes encoding TFIIS-related proteins in human cells. We have focused upon the genomic organization of one family member expressed primarily in the testis. This gene encodes a transcription elongation factor similar to but distinct from that encoded by a previously reported TFIIS gene. Also in contrast to the previously reported TFIIS gene, the testis gene contains introns. All exon-intron junction sequences match the consensus GT/AG rule. The gene consists of seven exons and six introns with a total size of approximately 7 kb. The nucleotide sequence of the 5 flanking region of the testis TFIIS gene contains several potential regulatory factor-binding sites, not all of which are present in the TFIIS gene, whose expression is nearly ubiquitous. Elucidation of the full structure of the testis TFIIS gene should be useful for determining its chromosomal localization and its potential role in the regulation of gene expression in human tissues.
