Immunohistochemical localization of betacellulin, a new member of the EGF family, in normal human pancreas and islet tumor cells

Immunohistochemical localization of betacellulin, a new member of the EGF family, in normal human pancreas and islet tumor cells
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DOI:
10.1507/endocrj.46.755
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发表时间:
1999-12-01
期刊:
影响因子:
2
通讯作者:
Matsuzawa, Y
Matsuzawa, Y
中科院分区:
医学4区
文献类型:
--
作者:
Miyagawa, J;Hanafusa, T;Matsuzawa, Y

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β细胞素(Betacellulin,BTC)是从小鼠β细胞瘤(betaTC-3)中分离纯化的表皮生长因子(epidermalgrowthfactor,EGF)家族的新成员,可与受体酪氨酸激酶、EGF受体(erbB 1)和erbB 4结合。已证实proBTC mRNA在人胰腺组织中大量表达,ETC可将分泌淀粉酶的大鼠腺泡细胞系(AR 42 J)转化为胰岛素分泌细胞,表明ETC可能对胰岛细胞的生长和/或分化具有重要作用。然而,胰腺中产生ETC的细胞类型尚未阐明。在这项研究中,我们研究了ETC在人类胰腺和胰岛细胞肿瘤中的定位。免疫组化使用特异性抗体的人ETC显示,这种蛋白质产生于α细胞和导管细胞,并可能在β细胞在正常成人胰腺。EGF受体(erbB 1)和erbB 4主要表达于胰岛和胰管细胞以及胰管细胞。这些结果表明ETC及其受体的定位,并表明ETC可能是具有生理重要作用的因素之一,如人胰腺中胰岛细胞的生长和分化。
Betacellulin (BTC) purified from mouse beta cell tumor (beta TC-3) is a new member of the epidermal growth factor (EGF) family which can bind receptor tyrosine kinase, EGF receptor (erbB1) and erbB4. It has been demonstrated that proBTC mRNA was abundantly expressed in human pancreas tissue, and that ETC converted amylase-secreting rat acinar cell line (AR42J) into insulin-secreting cells, suggesting that ETC might be important for the growth and/or differentiation of islet cells. However, the cell type producing ETC in the pancreas has not been clarified. In this study, we examined the localization of ETC in human pancreas and islet cell tumors. Immunohistochemistry using specific antibodies to human ETC revealed that this protein was produced in alpha cells and duct cells, and probably in beta cells in normal adult pancreas. Furthermore, strong immunoreactivity to ETC was detected in primitive duct cells of the fetal pancreas, and both insulinoma and glucagonoma cells also showed positive immunoreactivity to ETC. EGF receptor (erbB1) and erbB4 were expressed mainly in islet and duct cells, and duct cells, respectively. These results demonstrate the localization of ETC and its receptors, and suggest that ETC may be one of the factors that have physiologically important roles such as growth and differentiation of islet cells in the human pancreas.