期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：20
页码：11400-11405
DOI：10.1073/pnas.1534601100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A considerable body of circumstantial data suggests that cyclin D1 is an attractive candidate to mediate the effects of {beta}-catenin in mammary tissue. To test the functional significance of these correlative findings, we investigated the genetic interaction between transcriptionally active {beta}-catenin ({Delta}N89{beta}-catenin) and its target gene cyclin D1 in the mouse mammary gland during pubertal development, pregnancy, and tumorigenesis. Our data demonstrate that cyclin D1 is dispensable for the {Delta}N89{beta}-catenin-stimulated initiation of alveologenesis in virgin females, for the de novo induction of alveoli in males, and for the formation of tumors. Indeed, lack of cyclin D1 accentuates and enhances these hyperplastic and tumorigenic {Delta}N89{beta}-catenin phenotypes. Although alveologenesis is initiated by {Delta}N89{beta}-catenin in a cyclin D1-independent fashion, up-regulation of cyclin D1 occurs in {Delta}N89{beta}-catenin mice and its expression remains essential for the completion of alveolar development during the later stages of pregnancy. Thus, alveologenesis is a two-step process, and cyclin D1 activity during late alveologenesis cannot be replaced by the activity of other {beta}-catenin target genes that successfully drive proliferation at earlier stages.
