期刊
MOLECULAR ENDOCRINOLOGY
卷 19, 期 3, 页码 574-587出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/me.2004-0287
关键词
-
资金
- NCI NIH HHS [CA26869, F32 CA90073] Funding Source: Medline
Progesterone receptors (PRs) are prognostic markers in breast cancers irrespective of the patient's progestational status. However, there are two PR isoforms, PR-A and PR-B, that are equimolar in the normal breast but dysregulated in advanced disease. Postmenopausal, tamoxifen-treated patients with estrogen receptor ( ER)positive, PR-A-rich tumors have much faster disease recurrence than patients with PR-B-rich tumors. To study the mechanisms we engineered ER+ breast cancer cells that express each PR isoform under control of an inducible promoter. We identified 79 genes regulated by progesterone ( P), mainly by PR-B, and 51 genes regulated without progesterone, mainly by PR-A. Only nine genes were regulated with and without ligand, leading to definition of three classes: I) genes regulated only by liganded PR; II) genes regulated only by unliganded PR; III) genes regulated by both. Unliganded PR-A and PR-B differentially regulate genes that coordinate extracellular signaling pathways and influence tumor cell biology. Indeed, in the absence of P, compared with ER+/PR-B+ or PR- cells, ER+, PR-A+ cells exhibit an aggressive phenotype, are more adhesive to an extracellular matrix, and are more migratory. Additionally, unliganded PR- A and PR- B both inhibit cell growth and provoke resistance to Taxol-induced apoptosis. We propose that PR- A: PR- B ratios, even in the absence of P, influence the biology and treatment response of ER+ tumors, that PR- A isoforms are functionally dominant in P-deficient states, and that PR- A rich tumors are especially aggressive.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据