Mould Richard, Pondel Marc D
St, George's Hospital Medical School Dept, of Cellular Pathology London, SW17 ORE, United Kingdom.
Cancer Cell Int. 2003 Apr 25;3(1):6. doi: 10.1186/1475-2867-3-6.
The peptide hormone calcitonin (CT) can significantly effect the proliferation rate of CT receptor (CTR) positive human cancer cells. We wish to identify additional human cancers expressing CTRs and assay the effects of CT on their growth rates and signal transduction pathways. RESULTS: The expression of the human calcitonin receptor (hCTR) gene in the chronic myelogenous leukemia cell line K562 was examined. RT-PCR on total RNA extracted from K562 cells detected the presence of hCTR mRNA. Further analysis demonstrated that multiple hCTR isoforms were present. Incubation of K562 cells with salmon calcitonin (sCT), but not amylin, caused an increase in intracellular levels of cAMP similar to that induced by forskolin treatment. We further demonstrated that butyrate induced erythroid differentiation of K562 cells caused a significant decrease in hCTR mRNA levels. However, phorbol myristate acetate (PMA) induced megakaryocytic differentiation of these cells had no significant effect on hCTR mRNA levels. We demonstrated that exposure to various concentrations of sCT had no effect on the cellular proliferation of K562 cells in vitro. CONCLUSION: Chronic myelogenous k562 cells express multiple CTR isoforms. However, CT does not effect K562 proliferation rates. It is likely that the small increase in intracellular levels of cAMP following CT treatment is not sufficient to interfere with cellular growth.
肽激素降钙素(CT)可显著影响降钙素受体(CTR)阳性人类癌细胞的增殖速率。我们希望鉴定出其他表达CTR的人类癌症,并检测CT对其生长速率和信号转导途径的影响。结果:检测了慢性髓性白血病细胞系K562中人降钙素受体(hCTR)基因的表达。对从K562细胞中提取的总RNA进行逆转录聚合酶链反应(RT-PCR),检测到hCTR mRNA的存在。进一步分析表明存在多种hCTR亚型。用鲑鱼降钙素(sCT)而非胰淀素孵育K562细胞,导致细胞内cAMP水平升高,类似于福司可林处理诱导的升高。我们进一步证明,丁酸盐诱导K562细胞向红系分化导致hCTR mRNA水平显著降低。然而,佛波酯肉豆蔻酸酯(PMA)诱导这些细胞向巨核系分化对hCTR mRNA水平没有显著影响。我们证明,暴露于不同浓度的sCT对体外K562细胞的增殖没有影响。结论:慢性髓性K562细胞表达多种CTR亚型。然而,CT不影响K562的增殖速率。CT处理后细胞内cAMP水平的小幅升高可能不足以干扰细胞生长。