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骨桥蛋白在乳腺发育和肿瘤发生中的表达。

Osteopontin expression in mammary gland development and tumorigenesis.

作者信息

Rittling S R, Novick K E

机构信息

Department of Cell, Developmental, and Neurobiology, Rutgers University, Piscataway, New Jersey 08855, USA.

出版信息

Cell Growth Differ. 1997 Oct;8(10):1061-9.

PMID:9342184
Abstract

Osteopontin (OPN) is a secreted phosphoprotein that binds to cells via an Arg-Gly-Asp sequence and to mineralized surfaces. The protein can mediate cell adhesion and is strongly implicated in transformation and tumorigenesis. We have examined the expression pattern of OPN in mouse mammary glands at different stages of postnatal development. Whereas OPN is expressed at low-to-moderate levels in mammary glands from virgin and pregnant mice, the levels of OPN mRNA are extremely high in the lactating gland, consistent with the presence of the protein in milk. Expression is highest at 2 days of lactation and declines thereafter, but it remains high through involution. OPN expression is restricted to small nests or groups of cells at 9 days of involution. These results suggest that OPN may play a specific role in the process of involution that may be distinct from its role during lactation. In mammary tumors arising spontaneously in transgenic mice expressing the oncogenes c-myc and/or v-Ha-ras under the control of the mouse mammary tumor virus promoter, the level of OPN expression is increased dramatically over that in the normal gland in these same animals. Numerous cells expressing OPN mRNA are widespread throughout the tumors. OPN protein is detectable by Western blotting in extracts from the mammary gland at 2 days of lactation and from the tumors, but not in mammary glands at other stages of development. We hypothesize that OPN is exported from most tissues and that the protein is only detectable in tissues elaborating fluids, such as the lactating mammary gland, or in pathological situations when expression of OPN is abnormally high, such as in tumors.

摘要

骨桥蛋白(OPN)是一种分泌型磷蛋白,它通过精氨酸 - 甘氨酸 - 天冬氨酸序列与细胞结合,并与矿化表面结合。该蛋白可介导细胞黏附,且与细胞转化和肿瘤发生密切相关。我们研究了出生后不同发育阶段小鼠乳腺中OPN的表达模式。在未孕和怀孕小鼠的乳腺中,OPN以低到中等水平表达,而在泌乳期乳腺中,OPN mRNA水平极高,这与乳汁中存在该蛋白一致。在泌乳第2天表达最高,此后下降,但在退化期仍保持较高水平。在退化第9天,OPN表达局限于小巢状或细胞群。这些结果表明,OPN可能在退化过程中发挥特定作用,这可能与其在泌乳期的作用不同。在由小鼠乳腺肿瘤病毒启动子控制下表达癌基因c-myc和/或v-Ha-ras的转基因小鼠自发产生的乳腺肿瘤中,OPN的表达水平比这些相同动物的正常腺体中显著增加。许多表达OPN mRNA的细胞广泛分布于肿瘤中。通过蛋白质印迹法可在泌乳第2天的乳腺提取物和肿瘤提取物中检测到OPN蛋白,但在其他发育阶段的乳腺中未检测到。我们推测OPN从大多数组织中输出,并且该蛋白仅在分泌液体的组织中可检测到,如泌乳期的乳腺,或在OPN表达异常高的病理情况下,如肿瘤中。

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