PROTO-ONCOGENES IN GAMETOGENESIS AND EARLY DEVELOPMENT

配子发生和早期发育中的原癌基因

• 批准号: 3328087
• 负责人: GEOFFREY M COOPER
• 金额: $ 28.74万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3328087
• 关键词: antisense nucleic acid; developmental genetics; early embryonic stage; embryo /fetus; fluorescent dye /probe; gene expression; genetic regulatory element; genetic transcription; genetically modified animals; germ cells; laboratory mouse; laboratory rabbit; oogenesis; protein biosynthesis; protooncogene; spermatogenesis; transcription factor; western blottings

The overall goal of the proposed research is investigation of the potential roles of proto-oncogenes in mammalian gametogenesis and early embryonic development. The c-mos c-abi and int-1 proto-oncogenes are transcribed during specific stages of spermatogenesis in the mouse. In addition, c-mos is transcribed in growing oocytes and high levels of c- mos RNA are accumulated by the germinal vesicle stage. The oocyte c-mos RNA is post-transcriptionally polyadenylated in concert with oocyte maturation and is degraded by the mid to late two cell stage, suggesting possible roles for c-mos as a maternal message. Since c-mos represents the first candidate for a regulatory maternal RNA unique to oocytes, further studies with its expression in spermatogenesis. Synthesis, phosphorylation and stability of the c-mos protein will be studied in spermatocytes, oocytes, eggs and embryos. The biological functions of c- mos in oocytes will be investigated by inhibiting c-mos expression using anti-sense oligonucleotides and/or anti-mos antibodies. These studies will be correlated with alterations in protein phosphorylation to identify candidate targets for c-mos protein kinase activity. Regulatory sequences and trans-acting factors which control c-mos expression during maturation of spermatocytes and oocytes will be investigated and the developmental specificity of c-mos expression in spermatogenesis will be further studied. The expression of additional selected proto-oncogenes will be studied in spermatogenesis, oogenesis and pre-implantation mouse embryos. These studies of normal proto-oncogene function in development will also contribute to understanding the mechanisms by which oncogenes induce neoplastic transformation.

拟议研究的总体目标是调查 原癌基因在哺乳动物配子发生和早期的潜在作用 胚胎发育。 c-mos c-abi 和 int-1 原癌基因是 在小鼠精子发生的特定阶段转录。在 此外，c-mos 在生长的卵母细胞中转录，并且高水平的 c- mos RNA 在生发囊泡阶段积累。卵母细胞c-mos RNA 与卵母细胞一起在转录后进行聚腺苷酸化 成熟并在两细胞阶段中后期降解，表明 c-mos 作为母性信息的可能作用。由于c-mos代表 卵母细胞特有的调节性母体 RNA 的第一个候选者， 进一步研究其在精子发生中的表达。合成， c-mos 蛋白的磷酸化和稳定性将在 精母细胞、卵母细胞、卵子和胚胎。 c-的生物学功能 将通过抑制 c-mos 表达来研究卵母细胞中的 mos 反义寡核苷酸和/或抗mos抗体。这些研究 与蛋白质磷酸化的改变相关 确定 c-mos 蛋白激酶活性的候选靶标。监管 控制 c-mos 表达的序列和反式作用因子 将研究精母细胞和卵母细胞的成熟，并 c-mos 表达在精子发生中的发育特异性将是 进一步研究。其他选定原癌基因的表达 将在小鼠的精子发生、卵子发生和植入前研究 胚胎。这些关于发育过程中正常原癌基因功能的研究 还将有助于理解癌基因的机制 诱导肿瘤转化。