Expression of TGF‐β type II receptor antisense RNA impairs TGF‐β signaling in vitro and promotes mammary gland differentiation in vivo

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Abstract
In order to clarify the role of TGF‐β in mammary development and tumorigenesis, we investigated the efficacy of full‐ or partial‐length TβRII antisense RNA specifically to reduce TβRII levels in both in vitro and in vivo model systems. Here we show that the expression of TβRII antisense RNA in vitro reduced TβRII cell surface expression and inhibited the antiproliferative and transcriptional responses to exogenous TGF‐β. Expression of full‐length TβRII 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 TβRII plays a critical role in maintaining the nondifferentiated character of virgin mammary gland epithelium.