Assuntos
Sistemas de Transporte de Aminoácidos Neutros/química , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Domínios e Motivos de Interação entre Proteínas , Treonina/fisiologia , Sequência de Aminoácidos , Sistemas de Transporte de Aminoácidos Neutros/genética , Animais , Transporte Biológico/genética , Feminino , Proteínas de Insetos/genética , Ativação do Canal Iônico/genética , Manduca , Potenciais da Membrana/genética , Oócitos , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas/genética , Treonina/química , Treonina/genética , Xenopus laevisRESUMO
PURPOSE: We used conventional cytogenetics, molecular cytogenetics, and molecular genetic analyses to study the pattern of allelic loss on chromosome 6q in a cohort of borderline epithelial ovarian tumors. EXPERIMENTAL DESIGN: Fifteen tumor samples were collected from patients undergoing surgery for ovarian tumors. The tumors of borderline malignancy, classified according to the standard criteria, included 4 mucinous and 11 serous tumors. Cytogenetic and molecular cytogenetic (with yeast artificial chromosome clones from 6q26-27) studies were performed on tumor areas contiguous to those used for histological examination ensuring the appropriate sampling. Moreover loss of heterozygosity analysis was performed using PCR amplification of eight microsatellite markers mapping on 6q27 (D6S193, D6S297), 6q26 (D6S305, D6S415, D6S441), 6q21 (D6S287), 6q16 (D6S311), and 6q14 (D6S300). RESULTS: Deletions of this chromosome arm, in particular of 6q24-27, were the most frequent lesions found in this set of tumors. In a tumor with a normal karyotype the only detectable alteration was a deletion of approximately 300 kb within the D6S149-D6S193 interval at band 6q27. This is, to date, the smallest deletion described for borderline tumors. CONCLUSION: Alterations in the above-mentioned interval are a common finding in advanced ovarian carcinomas but also in benign ovarian cysts, implying that some tumors of borderline malignancy may arise from benign tumors and that malignant ones may evolve from tumors of borderline malignancy. Genes located in 6q27 seem to be crucial for this mechanism of early events in ovarian tumorigenesis.
Assuntos
Adenocarcinoma Mucinoso/patologia , Deleção Cromossômica , Cromossomos Humanos Par 6/genética , Cistadenoma Seroso/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/genética , Bandeamento Cromossômico , Cistadenoma Seroso/genética , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Perda de Heterozigosidade , Repetições de Microssatélites , Neoplasias Ovarianas/genéticaRESUMO
Cytogenetic, molecular and functional analysis has shown that chromosome region 6q27 harbors a senescence inducing gene and a tumor suppressor gene involved in several solid and hematologic malignancies. We have cloned at 6q27 and characterized the RNASE6PL gene which belongs to a family of cytoplasmic RNases highly conserved from plants, to man. Analysis of 55 primary ovarian tumors and several ovarian tumor cell lines indicated that the RNASE6PL gene is not mutated in tumor tissues, but its expression is significantly reduced in 30% of primary ovarian tumors and in 75% of ovarian tumor cell lines. The promoter region of the gene was unaffected in tumors cell lines. Transfection of RNASE6PL cDNA into HEY4 and SG10G ovarian tumor cell lines suppressed tumorigenicity in nude mice. When tumors were induced by RNASE6PL-transfected cells, they completely lacked expression of RNASE6PL cDNA. Tumorigenicity was suppressed also in RNASE6PL-transfected pRPcT1/H6cl2T cells, derived from a human/mouse monochromosomic hybrid carrying a human chromosome 6 deleted at 6q27. Moreover, 63.6% of HEY4 clones and 42.8% of the clones of XP12ROSV, a Xeroderma pigmentosum SV40-immortalized cell line, transfected with RNASE6PL cDNA, developed a marked senescence process during in vitro growth. We therefore propose that RNASE6PL may be a candidate for the 6q27 senescence inducing and class II tumor suppressor gene in ovarian cancer.
Assuntos
Carcinoma/genética , Cromossomos Humanos Par 6/genética , Genes Supressores de Tumor , Neoplasias Ovarianas/genética , Ribonucleases/genética , Proteínas Supressoras de Tumor , Animais , Senescência Celular/genética , Clonagem Molecular , Ilhas de CpG , Metilação de DNA , Feminino , Humanos , Células Híbridas , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , RNA de Transferência de Serina , Distribuição TecidualRESUMO
Virgin female rats were kept in rooms where temperature was about 5 degrees C higher or lower than standard rearing temperature for two weeks before mating and during pregnancy. Acclimatation to changed environmental conditions caused reproductive alterations: ovulation increase; decrease of implanting blastocists and/or viable foetuses; developmental defects.
