Tsuei B J, Povoski S P, Zhou W, Bell R H
Department of Veterans Affairs Medical Center, Seattle, WA 98108, USA.
Pancreas. 1996 Nov;13(4):401-6. doi: 10.1097/00006676-199611000-00010.
The peptide hormone cholecystokinin (CCK) has been shown to stimulate the growth of azaserine-induced preneoplastic nodules in the rat pancreas. Previously, our labortory demonstrated by classical binding studies that CCK receptors are overexpressed in azaserine-induced rat pancreatic neoplasms. In the present study, we utilized autoradiography to determine the temporal course of this increased receptor binding. Male Lewis rats were given azaserine or saline injections and sacrificed at 2, 4, 8, 12, and 18 months of age. Pancreatic tissue was harvested and autoradiography using 125l-labeled. CCK-8 was performed. Densitometry measurements of azaserine-induced pancreatic nodules, internodular pancreas, and normal pancreatic tissue (from saline-treated controls) of each age group were taken with an image analyzer. There was no statistically significant difference in CCK binding to internodular pancreas and normal pancreas at any age. At 2 months of age, there was no significant increase in CCK binding to azaserine-induced pancreatic nodules. However, at 4, 8, 12, and 18 months of age there was significantly greater CCK binding to azaserine-induced pancreatic nodules than to both internodular pancreas and normal pancreas (p < 0.001 for all groups). At 18 months of age, one azaserine-treated animal developed a pancreatic acinar cell carcinoma, which likewise exhibited significantly greater CCK binding than internodular pancreas or normal pancreas (p < 0.001 for both). These findings demonstrate increased CCK binding in azaserine-induced preneoplastic pancreatic nodules and pancreatic acinar cell carcinoma, compatible with our previous demonstration of receptor overexpression in these tissues. Increased CCK binding first becomes apparent by 4 months following exposure to azaserine. These result suggest that overexpression of CCK receptors, located specifically on preneoplastic and neoplastic pancreatic lesions, results in increased CCK binding and is involved in the mediation of CCK-stimulated growth during azaserine-induced pancreatic carcinogenesis.
肽激素胆囊收缩素（CCK）已被证明可刺激大鼠胰腺中氮杂丝氨酸诱导的癌前结节生长。此前，我们实验室通过经典结合研究表明，CCK受体在氮杂丝氨酸诱导的大鼠胰腺肿瘤中过度表达。在本研究中，我们利用放射自显影术来确定这种受体结合增加的时间进程。给雄性Lewis大鼠注射氮杂丝氨酸或生理盐水，并在2、4、8、12和18月龄时处死。采集胰腺组织并使用125I标记的CCK-8进行放射自显影。用图像分析仪对每个年龄组的氮杂丝氨酸诱导的胰腺结节、结节间胰腺和正常胰腺组织（来自生理盐水处理的对照）进行光密度测量。在任何年龄，CCK与结节间胰腺和正常胰腺的结合均无统计学显著差异。在2月龄时，CCK与氮杂丝氨酸诱导的胰腺结节的结合没有显著增加。然而，在4、8、12和18月龄时，CCK与氮杂丝氨酸诱导的胰腺结节的结合显著高于结节间胰腺和正常胰腺（所有组p<0.001）。在18月龄时，一只接受氮杂丝氨酸处理的动物发生了胰腺腺泡细胞癌，其CCK结合同样显著高于结节间胰腺或正常胰腺（两者p<0.001）。这些发现表明，在氮杂丝氨酸诱导的癌前胰腺结节和胰腺腺泡细胞癌中CCK结合增加，这与我们之前在这些组织中证明的受体过度表达一致。CCK结合增加在接触氮杂丝氨酸后4个月时首次变得明显。这些结果表明，特异性位于癌前和肿瘤性胰腺病变上的CCK受体过度表达导致CCK结合增加，并参与氮杂丝氨酸诱导的胰腺癌发生过程中CCK刺激的生长调节。
