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血清白蛋白和甲胎蛋白在小鼠正常及肿瘤性原始胚胎结构中的表达

Expression of serum albumin and of alphafetoprotein in murine normal and neoplastic primitive embryonic structures.

作者信息

Trojan J, Naval X, Johnson T, Lafarge-Frayssinet C, Hajeri-Germond M, Farges O, Pan Y, Uriel J, Abramasky O, Ilan J

机构信息

IRSC-CNRS, Hopital Paul Brosse, Villejuif, France.

出版信息

Mol Reprod Dev. 1995 Dec;42(4):369-78. doi: 10.1002/mrd.1080420402.

Abstract

Alphafetoprotein (AFP), a major serum protein synthesized during the embryo-fetal and postnatal period (in the yolk sac, then in the liver), is also an oncoprotein. The intracellular presence of AFP and of serum albumin (SA) in normal and neoplastic neural crest and neural tube derivatives was previously demonstrated. In this work we have studied the comparative expression of AFP and SA in primitive neuroectoblastic structures of mouse embryos (6 and 7 days "post coitum") and mouse teratocarcinomas (derived from the PCC4 cell line). Using immunofluorescence technique, antibodies to SA gave a positive reaction in embryos of 7 days, while AFP was not detected during this period. By mRNA in situ hybridization, SA mRNA gave a strong signal in both 6 and 7 day embryos, whereas AFP mRNA gave a weak signal only in 7-day embryos. The distribution of SA and AFP and their mRNAs was investigated in primitive neuroectoblastic structures of the teratocarcinomas by in situ hybridization and immunostaining. Only SA protein was detectable by immunostaining. SA mRNA gave a strong signal in differentiating structures as well as in undifferentiated cell clusters. AFP mRNA was observed only in differentiating structure. Dot-blot hybridization indicated that the level of SA transcripts was at least 6-fold higher than that of AFP transcripts in the teratocarcinomas investigated. In teratocarcinoma-bearing mice injected intraperitoneally with 125I-radiolabeled SA and AFP, significant accumulations of both SA and AFP were demonstrated in the tumors, SA being about 3-fold higher than that of AFP after normalization to quantity of uptake in liver. External in vivo photoscanning confirmed this relationship of accumulated radiolabeled proteins. The last observation could be useful in vivo for diagnosis of teratocarcinoma. We conclude that the expression of SA relative to AFP and the external cellular uptake of SA relative to AFP are similar in normal embryonic developing tissues and in the corresponding morphologically neoplastic tissues of the teratocarcinomas. The same SA:AFP relationship constitutes an oncofetal marker of primitive neuroectoblastic structures.

摘要

甲胎蛋白(AFP)是胚胎-胎儿期及出生后(在卵黄囊,然后在肝脏)合成的一种主要血清蛋白,也是一种癌蛋白。先前已证明正常和肿瘤性神经嵴及神经管衍生物中存在细胞内AFP和血清白蛋白(SA)。在这项工作中,我们研究了AFP和SA在小鼠胚胎(“合子后”6天和7天)和小鼠畸胎瘤(源自PCC4细胞系)的原始神经外胚层结构中的比较表达。使用免疫荧光技术,抗SA抗体在7天的胚胎中产生阳性反应,而在此期间未检测到AFP。通过mRNA原位杂交,SA mRNA在6天和7天的胚胎中均产生强信号,而AFP mRNA仅在7天的胚胎中产生弱信号。通过原位杂交和免疫染色研究了畸胎瘤原始神经外胚层结构中SA和AFP及其mRNA的分布。通过免疫染色仅可检测到SA蛋白。SA mRNA在分化结构以及未分化细胞簇中产生强信号。仅在分化结构中观察到AFP mRNA。斑点印迹杂交表明,在所研究的畸胎瘤中,SA转录本水平比AFP转录本水平至少高6倍。在腹腔注射125I放射性标记的SA和AFP的荷畸胎瘤小鼠中,肿瘤中显示出SA和AFP均有明显蓄积,将肝脏摄取量标准化后,SA比AFP高约3倍。体外体内光扫描证实了放射性标记蛋白蓄积的这种关系。最后的观察结果可能对畸胎瘤的体内诊断有用。我们得出结论,在正常胚胎发育组织和畸胎瘤相应形态学肿瘤组织中,SA相对于AFP的表达以及SA相对于AFP的细胞外摄取是相似的。相同的SA:AFP关系构成了原始神经外胚层结构的肿瘤胎儿标志物。

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