Expression of TGF-beta type II receptor antisense RNA impairs TGF-beta signaling in vitro and promotes mammary gland differentiation in vivo.
In order to clarify the role of TGF-beta in mammary development and tumorigenesis, we investigated the efficacy of full- or partial-length TbetaRII antisense RNA specifically to reduce TbetaRII levels in both in vitro and in vivo model systems. Here we show that the expression of TbetaRII antisense RNA in vitro reduced TbetaRII cell surface expression and inhibited the antiproliferative and transcriptional responses to exogenous TGF-beta. Expression of full-length TbetaRII antisense RNA in a transgenic mouse model under control of the mouse mammary tumor virus promotor resulted in precocious lobuloalveolar development of the mammary gland, a phenotype that resembles that of early pregnancy. These data demonstrate that TbetaRII plays a critical role in maintaining the nondifferentiated character of virgin mammary gland epithelium.
Receptor, Signaling and Proteomics Group, National Research Council, Biotechnology Research Institute, 6100 Royalmount Avenue, Montréal, Québec H4P 2R2, Canada.
Anne E G
AE
Lenferink
Joanne
J
Magoon
Marie-Claude
MC
Pepin
Alain
A
Guimond
Maureen D
MD
O'Connor-McCourt
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D002460:Cell Line; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D017403:In Situ Hybridization; D008156:Luciferases / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D008907:Mink; D017346:Protein Serine-Threonine Kinases; D016372:RNA, Antisense / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
D016372:RNA, Antisense; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II