Transgenic mice expressing a dominant-negative mutant type II transforming growth factor-β receptor exhibit impaired mammary development and enhanced mammary tumor formation

Agnieszka E. Gorska, Roy A. Jensen, Yu Shyr, Mary E. Aakre, Neil A. Bhowmick, Harold L. Moses

研究成果: Article同行評審

104 引文 斯高帕斯(Scopus)

摘要

We have previously shown that expression of a dominant-negative type II transforming growth factor-β receptor (DNIIR) in mammary epithelium under control of the MMTV promoter/enhancer causes alveolar hyperplasia and differentiation in virgin mice. Here we show that MMTV-DNIIR female mice have accelerated mammary gland differentiation during early pregnancy with impaired development during late pregnancy and lactation followed by delayed postlactational involution. Mammary tumors, mostly carcinoma in situ, developed spontaneously in the MMTV-DNIIR mice with a long median latency (27.5 months). Crossbreeding to MMTV-transforming growth factor (TGF)-α mice to obtain mice expressing both transgenes resulted in mammary tumor formation with a much shorter latency more similar to those expressing only the MMTV-TGF-α transgene (<10 months median latency). The major difference in mammary tumors arising in MMTV-TGF-α compared to bigenic MMTV-DNIIR/MMTV-TGF-α was the marked suppression of tumor invasion by DNIIR transgene expression. Invading carcinoma cells in both MMTV-DNIIR and bigenic animals showed loss of DNIIR transgene expression as determined by in situ hybridization. The data indicate that signaling from endogenous TGF-βs not only plays an important role in normal mammary gland physiology but also can also suppress the early stage of tumor formation and contribute to tumor invasion once carcinomas have developed.

原文English
頁(從 - 到)1539-1549
頁數11
期刊American Journal of Pathology
163
發行號4
DOIs
出版狀態Published - 2003 十月 1

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

指紋 深入研究「Transgenic mice expressing a dominant-negative mutant type II transforming growth factor-β receptor exhibit impaired mammary development and enhanced mammary tumor formation」主題。共同形成了獨特的指紋。

引用此