RESUMEN
A new case of trisomy 19q13.2-->qter is described in a male child which was caused by a maternal balanced translocation (13;19)(p13;q13.2). The major clinical features detected in the patient included the following: facial dysmorphism, bilateral coloboma, narrow and hypoplastic nails, cardiac malformations (Fallot's tetralogy), genitourinary and gastrointestinal anomalies, and agenesis of the corpus callosum. A comparison with other reported cases of partial trisomy 19q is presented. A hypothesis is proposed to account for the involvement of p13 regions of different acrocentrics in some cases of familial translocations involving a chromosome 19.
Asunto(s)
Cromosomas Humanos Par 19 , Translocación Genética/genética , Trisomía/genética , Femenino , Humanos , Cariotipificación , MasculinoRESUMEN
Estrogens induce transcriptional activation of c-fos and c-myc proto-oncogenes during mitogenic stimulation of human, chicken, mouse and rat cells in vivo and in vitro. In this paper we show that 17 beta-estradiol injected into adult ovariectomized rats increases c-jun, jun-B and jun-D gene transcription in the uterus. Kinetics and amplitude of response are different for each gene, since c-jun is activated first, within 30 min after injection, followed by jun-D and jun-B, 60 and 90 min after injection, respectively. Maximal activation of jun-B marks a drop in transcription of all the jun genes. Furthermore, transcriptional activation by 17 beta-estradiol of the growth-regulated beta- and gamma-cytoskeletal actin genes is prevented by an inhibitor of protein synthesis, indicating that it is a secondary response to the hormone. These data support the hypothesis that during growth stimulation of target cells the estrogen receptor induces transcription of regulatory genes, triggering in this way a cascade of gene regulation events that results in progression through the cell cycle.
Asunto(s)
Actinas/genética , Núcleo Celular/metabolismo , Estradiol/farmacología , Regulación de la Expresión Génica , Genes jun , Transcripción Genética , Útero/metabolismo , Animales , Núcleo Celular/efectos de los fármacos , Sondas de ADN , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Genes fos , Genes jun/efectos de los fármacos , Genes myc , Cinética , Ovariectomía , Poli A/genética , Poli A/aislamiento & purificación , ARN/genética , ARN/aislamiento & purificación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas , Transcripción Genética/efectos de los fármacos , Útero/efectos de los fármacosRESUMEN
17 beta-estradiol, a long acting estrogen that is mitogenic for rat uterus in vivo, or the short acting estrogens estriol and 16 alpha-estradiol, not mitogenic on their own, were injected into adult, castrated rats and their effect on uterine gene expression and rate of DNA synthesis were compared. All three compounds increased steady-state mRNA concentration of c-fos, c-jun and c-myc proto-oncogenes to comparable levels (2 hrs after treatment), whereas only 17 beta-estradiol was found to stimulate significantly DNA synthesis (20-22 hrs later). Based on the different retention time of the tested estrogens in rat tissues, it is concluded that a short exposure to the hormone is sufficient to render uterine cells competent to progress through the cell cycle, via activation of 'immediate-early' genes expression, but that stimulation of DNA synthesis requires further changes, achieved via a prolonged exposure of the cells to the estrogenic stimulus.
Asunto(s)
Proteínas de Unión al ADN/genética , ADN/biosíntesis , Estradiol/farmacología , Estriol/farmacología , Proteínas Proto-Oncogénicas/genética , Factores de Transcripción/genética , Útero/fisiología , Animales , Femenino , Expresión Génica/efectos de los fármacos , Ovariectomía , Proteínas Proto-Oncogénicas c-fos , Proteínas Proto-Oncogénicas c-jun , Proteínas Proto-Oncogénicas c-myc , ARN Mensajero/genética , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
Estrogen is a mitogen for the rat uterus, where it induces transient activation of c-fos and c-myc protooncogene expression, followed by increases in DNA synthesis and cell proliferation. JUN-C, the product of the c-jun protooncogene, is a nuclear protein that can interact with FOS to modulate the activity of AP-1-responsive promoters. To test whether c-jun is a target for estrogen regulation, we measured the effects of 17 beta-estradiol on the expression of this gene in rat uterus. A human c-jun cDNA probe detects in rat uterus two mRNA species of 2.5 and 3.2 kilobases. Treatment of the animals with estrogen results in a rapid transient increase in the concentrations of these mRNAs; a 4- to 5-fold increase over the prestimulation level was detected starting 30 min after estrogen injection and lasting for 2 h, with a return to the prestimulation level after 4 h. In accordance with the results obtained by analysis of the mRNA, we found that estrogen increases 3- to 4-fold c-jun gene transcription in the uterus, at the same time it induces its mRNA accumulation. The ability of estrogen to induce c-jun gene expression was not abolished by the protein synthesis inhibitor cycloheximide, suggesting that transcriptional activation of this protooncogene is a primary response to the hormone. Furthermore, we found that in the estrogen-responsive MCF-7 human mammary carcinoma cells, estrogen stimulates transcription of a reporter gene containing four copies of a jun/AP-1 response element. These data demonstrate that c-jun gene expression is regulated by estrogen and suggest that JUN-C could play a role in the activation of cell proliferation by estrogen.