al Moustafa A E, Raes M B, Saule S, Dieterlen-Lièvre F
Institut d'Embryologie Cellulaire et Moléculaire du CNRS et du Collège de France, Nogent s, Marne.
Cell Differ Dev. 1988 Nov;25(2):119-34. doi: 10.1016/0922-3371(88)90005-6.
The present study extends our previous data, showing that the v-myc oncogene induces heart tumors and skin anomalies in young avian embryos [Saule et al., Proc. Natl. Acad. Sci. USA 84, 7982-7986 (1987)]. We now report that the target cells which become transformed are the same, whether the MC29 retrovirus is injected at E3 in various sites of the embryo (coelom, heart, brain, lateral plate mesoderm) or deposited on the embryo. Furthermore we confirm, in the quail, the time-specific pattern previously observed in the chick. In the quail, the incidence of heart tumors falls from 100% to 28% when injection is delayed from E3 to E4. By contrast, the incidence of skin anomalies rises from 30% to 64% when injection is delayed from E3 to E4. The skin defect, which consists of the presence of bell-shaped cornified feathers, could be assigned to hyperkeratinization of the epidermis. Both the dermis and the epidermis displayed hyperproliferation, whereas skin muscle hypertrophy during the embryonic period could not be confirmed. The presence of myc gene products was investigated using an antibody that recognizes both the c- and v-myc proteins. In the skin of control embryos, nuclei were well stained at E12-E13. At E14 the signal had disappeared. In abnormal skin patches from infected embryos, the antibody still marked heavily epidermal and dermal nuclei at E18. Finally we injected MC29 through the chorioallantoic vein in E10 chickens. No tumors were found during embryonic life, but 81% of the chickens developed tumors of hemopoietic or endothelial origin from the 14th posthatching day onwards. Studies of MC29 integration sites demonstrated that these tumors were derived from only a few transformed cells. Thus, contrasting with in vitro experiments, in vivo this virus has a restricted number of targets varying with the time of injection.
本研究扩展了我们之前的数据，表明v-myc癌基因可在幼禽胚胎中诱发心脏肿瘤和皮肤异常[索勒等人，《美国国家科学院院刊》84, 7982 - 7986(1987)]。我们现在报告，无论MC29逆转录病毒是在胚胎发育第3天注射到胚胎的各个部位(体腔、心脏、脑、侧板中胚层)还是沉积在胚胎上，发生转化的靶细胞都是相同的。此外，我们在鹌鹑中证实了先前在小鸡中观察到的时间特异性模式。在鹌鹑中，当注射时间从胚胎发育第3天推迟到第4天时，心脏肿瘤的发生率从100%降至28%。相比之下，当注射时间从胚胎发育第3天推迟到第4天时，皮肤异常的发生率从30%升至64%。皮肤缺陷表现为出现钟形角质化羽毛，可归因于表皮的过度角化。真皮和表皮均显示细胞过度增殖，而胚胎期皮肤肌肉肥大无法得到证实。使用一种能识别c-myc和v-myc蛋白的抗体研究myc基因产物的存在情况。在对照胚胎的皮肤中, E12 - E13时细胞核染色良好。在E14时信号消失。在受感染胚胎的异常皮肤斑块中，该抗体在E18时仍能强烈标记表皮和真皮细胞核。最后，我们在胚胎发育第10天的鸡中通过尿囊绒膜静脉注射MC29。胚胎期未发现肿瘤，但从孵化后第14天起，81%的鸡发生了造血或内皮来源的肿瘤。对MC29整合位点的研究表明，这些肿瘤仅来源于少数转化细胞。因此，与体外实验不同，在体内这种病毒的靶细胞数量有限，且随注射时间而变化。
