三文鱼等食物中含有丰富的维生素D
维生素D可以减缓癌细胞进展，控制癌细胞的增殖。麦吉尔大学的一个研究团队发现了维生素D预防癌症作用的分子基础。麦吉尔大学生理学药学系的教授John White 和 David Goltzman领导这个团队发现具有生理活性的维生素D通过几种途径抑制cMYC的生成，阻碍其发挥作用。cMYC蛋白可促进细胞分裂，在超过半数的肿瘤内其活性上调。他们的研究结果发表在最新一期的《Proceedings of the National Academy of Sciences》上。
尽管从有限的食物来源以及通过春夏季节晒太阳即可获取维生素D，但是食物摄入贫乏，外加缺少阳光，导致全世界大部分人维生素D缺乏或不足。众所周知，维生素D生理作用广泛，一旦缺乏，其生理作用受到影响而癌症发生率增加。维生素D缺乏与癌症发生率增加的相关性对于消化道癌症尤其是结肠癌特别明显，另外某些类型的白血病亦是如此。
“多年来，我的实验室一直专注于维生素D在人癌细胞内的发挥作用的分子机制，尤其是其在抑制细胞增殖方面的作用，”Prof. White说。“我们发现维生素D可以调控cMYC蛋白的合成和降解速率。更重要的是，维生素D可以有效的促进MXD1—一种cMYC的天然拮抗剂的生成，从根本上阻断cMYC蛋白的功能。
这个小组将维生素D用于小鼠的皮肤，并观察到cMYC蛋白水平下调，发现其功能减弱的证据。然而，对于另外一些缺乏维生素D特异性的受体的小鼠，一些组织如皮肤和结肠表面的cMYC水平明显上调。
“总的来说，我们的结果显示维生素D可以遏制cMYC的功能，减缓癌细胞从癌变前转变为癌变状态的进程，从而抑制癌细胞增殖。我们希望这些结果可以鼓励人们维持补充足量维生素D，促成大型、控制良好的癌症化学预防实验，以研究足量补充维生素D的作用。”Dr. White. 说。
这项工作受到Canadian Institutes of Health Research and the National Cancer Institute/Canadian Cancer Society Research Institute的资助。
Vitamin D receptor as a master regulator of the c-MYC/MXD1 network
Reyhaneh Salehi-Tabar, Loan Nguyen-Yamamoto, Luz E. Tavera-Mendoza, Thomas Quail, Vassil Dimitrov, Beum-Soo An, Leon Glass, David Goltzman, and John H. White
Vitamin D signaling regulates cell proliferation and differentiation, and epidemiological data suggest that it functions as a cancer chemopreventive agent, although the underlying mechanisms are poorly understood. Vitamin D signaling can suppress expression of genes regulated by c-MYC, a transcription factor that controls epidermal differentiation and cell proliferation and whose activity is frequently elevated in cancer. We show through cell- and animal-based studies and mathematical modeling that hormonal 1,25-dihydroxyvitamin D (1,25D) and the vitamin D receptor (VDR) profoundly alter, through multiple mechanisms, the balance in function of c-MYC and its antagonist the transcriptional repressor MAD1/MXD1. 1,25D inhibited transcription of c-MYC–regulated genes in vitro, and topical 1,25D suppressed expression of c-MYC and its target setd8 in mouse skin, whereas MXD1 levels increased. 1,25D inhibited MYC gene expression and accelerated its protein turnover. In contrast, it enhanced MXD1 expression and stability, dramatically altering ratios of DNA-bound c-MYC and MXD1. Remarkably, F-box protein FBW7, an E3-ubiquitin ligase, controlled stability of both arms of the c-MYC/MXD1 push–pull network, and FBW7 ablation attenuated 1,25D regulation of c-MYC and MXD1 turnover. Additionally, c-MYC expression increased upon VDR knockdown, an effect abrogated by ablation of MYC regulator β-catenin. c-MYC levels were widely elevated in vdr−/− mice, including in intestinal epithelium, where hyperproliferation has been reported, and in skin epithelia, where phenotypes of VDR-deficient mice and those overexpressing epidermal c-MYC are similar. Thus, 1,25D and the VDR regulate the c-MYC/MXD1 network to suppress c-MYC function, providing a molecular basis for cancer preventive actions of vitamin D.
文献链接：Vitamin D receptor as a master regulator of the c-MYC/MXD1 network
