Baldwin R L, Friess H, Yokoyama M, Lopez M E, Kobrin M S, Büchler M W, Korc M
Department of Medicine, University of California, Irvine 92717, USA.
Int J Cancer. 1996 Jul 17;67(2):283-8. doi: 10.1002/(SICI)1097-0215(19960717)67:2<283::AID-IJC21>3.0.CO;2-B.
Transforming growth factor-beta (TGF-beta) receptors constitute a family of transmembrane proteins that bind TGF-beta ligands. In this study we assessed the growth responsiveness to TGF-beta 1 in pancreatic cancer cell lines and characterized the levels of expression of TGF-beta receptors in these cell lines and in human pancreatic cancer tissues. COLO 357 cells were most sensitive to the growth inhibitory actions of TGF-beta 1, PANC-1 cells exhibited moderate sensitivity, Hs766T cells exhibited slight sensitivity and MIA PaCa-2 and T3M4 cells were resistant to TGF-beta 1. Only COLO 357 cells expressed high levels of ALK5, the major type I TGF-beta receptor (T beta RI). Hs766T and PANC-1 cells expressed high levels of SKR1, another T beta RI subtype. Only MIA PaCa-2 cells did not exhibit the type II TGF-beta receptor (T beta-RII) transcript, whereas type III TGF-beta receptor (T beta-RIII) mRNA levels were elevated in this cell line and in HS766T cells. All the cell lines expressed TGF-beta 1, but TGF-beta 2 and TGF-beta 3 mRNA levels were variable. ALK5 and SKR1 mRNA levels were 6.8- and 9-fold greater in the pancreatic tumors in comparison with the corresponding levels in the normal pancreas. However, in the cancer cells, ALK5 immunoreactivity was faint, whereas T beta RII immunoreactivity was focal and intense. Conversely, in ductal cells adjacent to cancer cells ALK5 immunoreactivity was strong, whereas T beta RII immunoreactivity was weak. Since ALK5 heterodimerization with T beta RII is crucial for TGF-beta-mediated signaling, our findings suggest that low levels of ALK5 in pancreatic cancer cells within a tumor may protect against growth inhibition.
转化生长因子-β（TGF-β）受体构成了一类结合TGF-β配体的跨膜蛋白家族。在本研究中，我们评估了胰腺癌细胞系对TGF-β1的生长反应性，并对这些细胞系以及人胰腺癌组织中TGF-β受体的表达水平进行了表征。COLO 357细胞对TGF-β1的生长抑制作用最为敏感，PANC-1细胞表现出中等敏感性，Hs766T细胞表现出轻微敏感性，而MIA PaCa-2和T3M4细胞对TGF-β1具有抗性。只有COLO 357细胞表达高水平的ALK5，即主要的I型TGF-β受体（TβRI）。Hs766T和PANC-1细胞表达高水平的SKR1，这是另一种TβRI亚型。只有MIA PaCa-2细胞未表现出II型TGF-β受体（Tβ-RII）转录本，而III型TGF-β受体（Tβ-RIII）mRNA水平在该细胞系和HS766T细胞中升高。所有细胞系均表达TGF-β1，但TGF-β2和TGF-β3 mRNA水平各不相同。与正常胰腺中的相应水平相比，胰腺肿瘤中ALK5和SKR1 mRNA水平分别高6.8倍和9倍。然而，在癌细胞中，ALK5免疫反应性较弱，而TβRII免疫反应性呈局灶性且较强。相反，在癌细胞相邻的导管细胞中，ALK5免疫反应性较强，而TβRII免疫反应性较弱。由于ALK5与TβRII的异源二聚化对于TGF-β介导的信号传导至关重要，我们的研究结果表明，肿瘤内胰腺癌细胞中低水平的ALK5可能有助于防止生长抑制。
