Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109, USA.
Histol Histopathol. 2011 Jun;26(6):769-79. doi: 10.14670/HH-26.769.
A role for calcium in epithelial growth control is well-established in the colon and other tissues. In the colon, Ca²+ "drives" the differentiation process. This results in sequestration of β-catenin in the cell surface / cytoskeletal complex, leaving β-catenin unavailable to serve as a growth-promoting transcription enhancer in the nucleus. The signaling events that lead from Ca²+ stimulation to differentiation are not fully understood. A critical role for the extracellular calcium-sensing receptor (CaSR) is assumed, based on CaSR localization to the differentiating epithelial cells in the normal colonic mucosa (upper half of the crypt and crypt surface), decreased CaSR expression in colon carcinoma, and the results from in vitro studies with colonic epithelial cell lines. While Ca²+ is well-accepted as a growth-regulating agent in the colon, suppression of cell proliferation is not complete. At least part of the reason for this is the inherent variability in Ca²+ responsiveness among individual epithelial cells. Of interest, colon epithelial cells that are resistant to the growth-regulating activity of Ca²+ alone are still responsive to Ca²+ in conjunction with other transition metals. Whether a multi-mineral approach will, ultimately, prove to be more effective than Ca²+ alone as a colon cancer chemopreventive agent remains to be seen, but certainly worth investigating.
钙在肠上皮细胞生长控制中的作用在结肠和其他组织中已经得到充分证实。在结肠中，Ca²+“驱动”分化过程。这导致β-连环蛋白被隔离在细胞表面/细胞骨架复合物中，使β-连环蛋白无法在核内充当促进生长的转录增强子。导致从 Ca²+刺激到分化的信号事件尚未完全理解。基于钙敏感受体（CaSR）在正常结肠黏膜（隐窝上半部分和隐窝表面）分化上皮细胞中的定位、结肠癌中 CaSR 表达的降低以及体外结肠上皮细胞系研究的结果，假设 CaSR 发挥关键作用。虽然 Ca²+被广泛认为是结肠中的生长调节因子，但对细胞增殖的抑制并不完全。部分原因至少是单个上皮细胞之间 Ca²+反应性的固有变异性。有趣的是，单独对 Ca²+的生长调节活性具有抗性的结肠上皮细胞仍然对 Ca²+与其他过渡金属联合作用有反应。多矿物质方法最终是否比 Ca²+单独作为结肠癌化学预防剂更有效，还有待观察，但肯定值得研究。
