Michalides R, Wagenaar E, Sluyser M
Cancer Res. 1982 Mar;42(3):1154-8.
Mammary tumors of GR mice acquire extra mammary tumor virus (MMTV) DNA information within their DNA during tumor growth and development. These extra MMTV genes have been used by us as genotypic markers to investigate the heterogeneity of GR mammary tumors and their loss of hormone dependence during serial transplantation. Our studies reveal that the various subpopulations of cells within individual GR mammary tumors are characterized by differences in number and location of acquired extra MMTV DNA fragments. Losses of certain of these extra MMTV DNA fragments occur when mammary tumors become hormone independent, indicating a loss of hormone-dependent cells. The study of MMTV DNA markers also reveals that low levels of autonomous cells are already present in some hormone-dependent mammary tumors at an early stage of their development. The genotypic analysis strongly indicates that mammary tumor progression is not due to phenotypic adaptation but to clonal selection of the more aggressive sublines.
GR小鼠的乳腺肿瘤在肿瘤生长和发育过程中，其DNA内会获得额外的乳腺肿瘤病毒（MMTV）DNA信息。我们已将这些额外的MMTV基因用作基因型标记，以研究GR乳腺肿瘤的异质性及其在连续移植过程中激素依赖性的丧失。我们的研究表明，单个GR乳腺肿瘤内的各种细胞亚群的特征在于获得的额外MMTV DNA片段的数量和位置存在差异。当乳腺肿瘤变得激素非依赖性时，某些这些额外的MMTV DNA片段会丢失，这表明激素依赖性细胞的丧失。对MMTV DNA标记的研究还表明，在某些激素依赖性乳腺肿瘤发育的早期阶段，已经存在低水平的自主细胞。基因型分析有力地表明，乳腺肿瘤的进展不是由于表型适应，而是由于更具侵袭性的亚系的克隆选择。
