Chooi K F, Carter D A, Biswas S, Lightman S L, Ho M Y, Murphy D
Neuropeptide Laboratory, Institute of Molecular and Cell Biology, Republic of Singapore.
Cancer Res. 1994 Dec 15;54(24):6434-40.
A transgenic mouse model has been developed to test the involvement of ectopic neuropeptide production as a secondary factor in cancer. Mice bearing a mouse mammary tumor virus-vasopressin (MMTV-VP) fusion transgene synthesized authentic vasopressin in mammary ducts and alveoli, but this had no effect on mammary gland development and growth. Mice bearing the MMTV-VP transgene were then mated with mice bearing the MMTV-Wnt-1 transgene to produce bitransgenic animals. Two types of mammary tumor develop in MMTV-Wnt-1 mice; type A mammary adenocarcinomas are uniform with fine acinar structure composed of small epithelial cells arranged to form round cavities and elongated tubules, while adenocarcinoma type B tumors have acinar areas, cystic spaces filled with blood or fluid, intracystic papillary projections, and cords as well as sheets of cells. Compared to the MMTV-Wnt-1 mice, the bitransgenic animals developed proportionally less type B tumors. Further, type B mammary adenocarcinomas from bitransgenic mice exhibited increased proliferation and growth, as judged by mitotic index and argyrophilic nucleolar organizer region counts, compared to type B tumors from MMTV-Wnt-1 mice. These data provide evidence that ectopic neuropeptide production can modulate the development of tumors in vivo.
已开发出一种转基因小鼠模型，以测试异位神经肽产生作为癌症的次要因素的参与情况。携带小鼠乳腺肿瘤病毒 - 加压素（MMTV - VP）融合转基因的小鼠在乳腺导管和腺泡中合成了真实的加压素，但这对乳腺发育和生长没有影响。然后将携带MMTV - VP转基因的小鼠与携带MMTV - Wnt - 1转基因的小鼠交配，以产生双转基因动物。MMTV - Wnt - 1小鼠会发生两种类型的乳腺肿瘤；A型乳腺腺癌形态一致，具有精细的腺泡结构，由排列成圆形腔和细长小管的小上皮细胞组成，而B型腺癌肿瘤有腺泡区域、充满血液或液体的囊性空间、囊内乳头状突起、条索以及细胞片。与MMTV - Wnt - 1小鼠相比，双转基因动物发生的B型肿瘤比例较低。此外，与来自MMTV - Wnt - 1小鼠的B型肿瘤相比，双转基因小鼠的B型乳腺腺癌通过有丝分裂指数和嗜银核仁组织区计数判断，显示出增殖和生长增加。这些数据提供了证据，表明异位神经肽产生可以在体内调节肿瘤的发展。
