Mas E, Abouakil N, Roudani S, Miralles F, Guy-Crotte O, Figarella C, Escribano M J, Lombardo D
INSERM-U.260, Faculté de Médecine, Marseille, France.
Biochem J. 1993 Jan 15;289 ( Pt 2)(Pt 2):609-15. doi: 10.1042/bj2890609.
A fetoacinar pancreatic protein (FAP) associated with the ontogenesis, differentiation and oncogenic transformation of the human exocrine pancreas has been purified from pancreatic juices of patients suffering from pancreatitis or duodenal cancers invading the pancreas [Escribano and Imperial (1989) J. Biol. Chem. 264, 21865-21871]. This protein has striking similarities, i.e. M(r), amino acid composition and N-terminal sequence, to the bile-salt-dependent lipase (BSDL) of normal human pancreatic secretion. The aim of this study was to gain further insight into the nature of the two proteins. Reactivity with the mouse monoclonal antibody J28 (mAb J28), which characterizes FAP, and enzyme activity could not be dissociated during biochemical purification of BSDL. Furthermore, a polyclonal antiserum raised against purified human BSDL reacted completely with FAP in Western-blot analysis giving additional support to the idea of similar molecular structures for BSDL and FAP. However, by the same technique, mAb J28 reacted with a relatively restricted population of BSDL molecules. The classical BSDL preparation could be separated into molecules bearing the J28 epitope and those devoid of it by immunoaffinity on immobilized mAb J28. The two subpopulations had identical N-terminal sequences and some differences in their amino acid compositions. However, they had different carbohydrate compositions. J28-epitope-bearing molecules were active on BSDL substrates, although their specific activity was decreased. These results are consistent with the existence of two closely related polypeptide chains with different glycan counterparts. Therefore, if the name FAP is reserved for molecules bearing the J28 epitope, which is linked to a carbohydrate-dependent structure. FAP could represent an oncofetal-related variant of BSDL. Our result is the first demonstration of the existence of an oncofetal-type subpopulation of an otherwise normally secreted human pancreatic enzyme.
一种与人类外分泌胰腺的个体发生、分化和致癌转化相关的胎儿腺泡胰腺蛋白（FAP）已从患有胰腺炎或侵犯胰腺的十二指肠癌患者的胰液中纯化出来[埃斯克里瓦诺和因佩里亚尔（1989年）《生物化学杂志》264卷，21865 - 21871页]。这种蛋白质与正常人胰腺分泌的胆汁盐依赖性脂肪酶（BSDL）在分子量、氨基酸组成和N端序列等方面具有显著相似性。本研究的目的是进一步深入了解这两种蛋白质的性质。在BSDL的生化纯化过程中，与表征FAP的小鼠单克隆抗体J28（mAb J28）的反应性和酶活性无法分离。此外，针对纯化的人BSDL产生的多克隆抗血清在蛋白质印迹分析中与FAP完全反应，这进一步支持了BSDL和FAP具有相似分子结构的观点。然而，通过相同技术，mAb J28与相对有限数量的BSDL分子发生反应。经典的BSDL制剂可以通过固定化mAb J28上的免疫亲和作用分离为带有J28表位的分子和不带有该表位的分子。这两个亚群具有相同的N端序列，氨基酸组成存在一些差异。然而，它们具有不同的碳水化合物组成。带有J28表位的分子对BSDL底物具有活性，尽管其比活性有所降低。这些结果与存在两条紧密相关但糖基部分不同的多肽链一致。因此，如果将FAP这个名称保留给带有与碳水化合物依赖性结构相关的J28表位的分子，那么FAP可能代表BSDL的一种癌胚相关变体。我们的结果首次证明了在正常分泌的人类胰腺酶中存在癌胚型亚群。
