Wang Lizhong, Liu Runhua, Ribick Mark, Zheng Pan, Liu Yang
Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine and Cancer Center, Ann Arbor, Michigan 48109, USA.
Discov Med. 2010 Oct;10(53):322-8.
The FOXP3 gene was initially identified because its mutation caused lethal autoimmune diseases in mice and humans. Mice with heterozygous mutations of FoxP3 (mouse version of the FOXP3 gene) succumb to mammary tumors spontaneously, while those with prostate-specific deletions develop prostate intraepithelial neoplasia. Somatic mutations, deletion, and epigenetic inactivation of FOXP3 are widespread among human breast and prostate cancers. Unlike autosomal tumor suppressor genes that are usually inactivated by mutations in both alleles, X-linked FOXP3 mutations in cancer samples are usually heterozygous, with the wildtype allele selectively inactivated in cancer. This skewed X-inactivation suggests a new approach to reactivation of FOXP3 for cancer therapy.
FOXP3基因最初是因为其突变在小鼠和人类中引发致死性自身免疫疾病而被发现的。携带FoxP3（FOXP3基因的小鼠版本）杂合突变的小鼠会自发患上乳腺肿瘤，而那些前列腺特异性缺失的小鼠则会发展为前列腺上皮内瘤变。FOXP3的体细胞突变、缺失和表观遗传失活在人类乳腺癌和前列腺癌中广泛存在。与通常因两个等位基因均发生突变而失活的常染色体肿瘤抑制基因不同，癌症样本中的X连锁FOXP3突变通常是杂合的，野生型等位基因在癌症中被选择性失活。这种偏向性的X染色体失活提示了一种重新激活FOXP3用于癌症治疗的新方法。
