Yamada Yasuhiro, Hata Kazuya, Hirose Yoshinobu, Hara Akira, Sugie Shigeyuki, Kuno Toshiya, Yoshimi Naoki, Tanaka Takuji, Mori Hideki
Department of Pathology, Gifu University School of Medicine, Gifu 500-8705, Japan. :
Cancer Res. 2002 Nov 15;62(22):6367-70.
Mutations in the human adenomatous polyposis coli (APC) gene are causative for familial adenomatous polyposis (FAP), a rare condition in which numerous colonic polyps arise during puberty and, if left untreated, lead to colon cancer. Mouse model for human FAP, Apc(Min/+) mouse, contains a truncating mutation in the Apc gene and spontaneously develops intestinal adenomas. However, the distribution of tumors along the intestine found in Apc(Min/+) mice is different from that in human FAP. A majority of intestinal polyps in the Apc(Min/+) mice is known to be located in the small intestine but rarely detected in the colon. We report here that adult Apc(Min/+) mice develop dozens of microadenomatous lesions in the colon (>20 lesions/colon). Surprisingly, the vast majority of such adenomatous lesions consisting of colonic crypts were <300 microm in their greatest dimension, whereas lesions in the small intestine showed various sizes. The allelic loss analysis revealed that these adenomatous crypts in the colon have already lost the remaining allele of Apc. Such findings suggest that, in contrast to tumorigenesis in the small intestine, loss of heterozygosity of the Apc gene is not sufficient for tumor development in the colon of Apc(Min/+) mice. Our results may give an account for the low incidence of colonic tumors in Apc(Min/+) mice.
人类腺瘤性息肉病 coli（APC）基因的突变是家族性腺瘤性息肉病（FAP）的病因，FAP 是一种罕见病症，患者在青春期会出现大量结肠息肉，若不治疗会发展为结肠癌。人类 FAP 的小鼠模型 Apc(Min/+)小鼠，其 Apc 基因存在截短突变，会自发形成肠道腺瘤。然而，Apc(Min/+)小鼠肠道肿瘤的分布与人类 FAP 不同。已知 Apc(Min/+)小鼠的大多数肠道息肉位于小肠，在结肠中很少检测到。我们在此报告，成年 Apc(Min/+)小鼠在结肠中会形成数十个微腺瘤性病变（>20 个病变/结肠）。令人惊讶的是，绝大多数由结肠隐窝组成的此类腺瘤性病变最大直径<300 微米，而小肠中的病变则呈现出各种大小。等位基因缺失分析显示，结肠中的这些腺瘤性隐窝已经丢失了 Apc 的剩余等位基因。这些发现表明，与小肠中的肿瘤发生不同，Apc 基因杂合性的丧失不足以在 Apc(Min/+)小鼠的结肠中引发肿瘤。我们的结果可能解释了 Apc(Min/+)小鼠结肠肿瘤发病率较低的原因。
