Christophe J
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Am J Physiol. 1994 Jun;266(6 Pt 1):G963-71. doi: 10.1152/ajpgi.1994.266.6.G963.
AR42J cells derive from azaserine-induced malignant nodules from the rat pancreas. They differ from normal acinar cells for at least three reasons: 1) they proliferate rapidly; 2) they synthesize, store, and secrete digestive enzymes but the regulation of their exocrine function is abnormal, from the emergence of atypical receptors (e.g., cholecystokinin octapeptide type B and pituitary adenylate cyclase-activating polypeptide type I receptors) to unusual inositol phosphate metabolism and cytoskeleton disorganization; and 3) they possess an added neuroendocrine-regulated pathway characterized by voltage-sensitive ionic currents, post-translational processing of peptidic prohormones (and possibly autocriny), and the release of small neurotransmitters (gamma-aminobutyric acid, glycine, and glutamic acid). These amphicrine cells represent, therefore, a cancerous version of the primordial pancreatic ductular epithelium. Dexamethasone favors their differentiation toward the exocrine phenotype. The mitogenic pathway is favored by the occupancy of receptor tyrosine kinases, adenosine 3',5'-cyclic monophosphate, ornithine decarboxylase expression, and Na(+)-H+ exchange. Somatostatin opposes proliferation through protein phosphatases.
AR42J细胞源自大鼠胰腺经重氮丝氨酸诱导产生的恶性结节。它们与正常腺泡细胞不同，原因至少有三点：1）它们增殖迅速；2）它们合成、储存和分泌消化酶，但外分泌功能的调节异常，从非典型受体（如B型八肽胆囊收缩素和I型垂体腺苷酸环化酶激活多肽受体）的出现到异常的肌醇磷酸代谢和细胞骨架紊乱；3）它们具有一条额外的神经内分泌调节途径，其特征为电压敏感性离子电流、肽类前激素的翻译后加工（可能还有自分泌）以及小神经递质（γ-氨基丁酸、甘氨酸和谷氨酸）的释放。因此，这些双分泌细胞代表了原始胰腺导管上皮的癌变形式。地塞米松有利于它们向外分泌表型分化。有丝分裂途径受到受体酪氨酸激酶的占据、3',5'-环磷酸腺苷、鸟氨酸脱羧酶表达和Na(+)-H+交换的促进。生长抑素通过蛋白磷酸酶抑制增殖。
