Al-Wadei Hussein A N, Majidi Mourad, Tsao Ming-Sound, Schuller Hildegard M
Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Cancer Genomics Proteomics. 2007 Jan-Feb;4(1):35-42.
Pancreatic ductal adenocarcinoma (PDAC) is among the most common causes of cancer death. Preclinical and clinical studies on the preventive effects of beta-carotene or other retinoids have used dietary supplements that yielded high systemic concentrations (1-50 microM). While some of the preclinical data suggested cancer preventive effects of these agents, they have disappointed in clinical investigations.
The effects of low concentrations (10 fM-200 nM)of beta-carotene on the proliferation, intracellular cAMP levels, PKA activation status and phosphorylation of EGFR-specific tyrosine kinases and ERK1/2 in immortalized human pancreatic duct epithelial cells was investigated.
Our data show significant concentration-dependent and PKA-dependent stimulation of all measured endpoints. Similar responses were achieved with forskolin. Our data indicate that low concentrations of beta-carotene stimulate the proliferation of the putative origin of PDAC, pancreatic duct epithelial cells via cAMP and PKA-dependent transactivation of the EGFR pathway. This could potentially have promoting effects on the development of PDAC.
胰腺导管腺癌（PDAC）是癌症死亡的最常见原因之一。关于β-胡萝卜素或其他类视黄醇预防作用的临床前和临床研究使用了能产生高全身浓度（1-50微摩尔）的膳食补充剂。虽然一些临床前数据表明这些药物具有癌症预防作用，但它们在临床研究中令人失望。
研究了低浓度（10飞摩尔-200纳摩尔）的β-胡萝卜素对永生化人胰腺导管上皮细胞增殖、细胞内cAMP水平、PKA激活状态以及EGFR特异性酪氨酸激酶和ERK1/2磷酸化的影响。
我们的数据显示，所有测量终点均有显著的浓度依赖性和PKA依赖性刺激。用福司可林也得到了类似的反应。我们的数据表明，低浓度的β-胡萝卜素通过cAMP和PKA依赖性的EGFR途径反式激活刺激PDAC假定起源细胞即胰腺导管上皮细胞的增殖。这可能对PDAC的发展具有促进作用。
