Collagen and @entity1421 regulate aromatase expression through the PI3K/ XXXX /IKK and the MAP kinase pathways in adipose stromal cells.

@entity172 @entity8047 @entity0 @entity5 @entity1421 @entity584 @entity2733 @entity11346 @entity23698 @entity1435
UNASSIGNED: Excessive local @entity172 production in the breast promotes @entity172 -dependent @entity0 . Aromatase is a key enzyme in @entity172 biosynthesis. Aromatase inhibitors used in the treatment of @entity0 are very effective, but indiscriminately reduce @entity172 synthesis in all tissues, causing major side  -effects. It is thus desirable to develop inhibitors that selectively block aromatase and @entity172 production in @entity0 . To this end, it is important to identify the mechanisms by which aromatase is activated in the @entity5 microenvironment. @entity1421  (PGE2) and collagen are two important factors in the @entity5 microenvironment, which contribute to @entity5 development and progression. In this study, we show that collagen  -induced aromatase expression in adipose stromal cells (ASCs) was significantly reduced by inhibitors of phosphatidylinositide 3  -kinase  (PI3K), IkB kinase (IKK), mitogen  -activated protein kinase kinase ( @entity8047 ), c  -Jun @entity2733  -terminal kinase  (JNK), protein kinase  A  (PKA), and by the knockdown of the @entity11346 and @entity23698 genes. In addition, PGE2  -induced aromatase expression was significantly inhibited by inhibitors of IKK, @entity8047 , JNK, @entity1435 and PKA. These results indicate that the PI3K/ @entity584 /IKK and the mitogen  -activated protein (MAP) kinase pathways are involved in collagen  - and PGE2  -induced aromatase expression, and also suggest that collagen and PGE2  -induced signaling pathways may crosstalk in regulating aromatase expression. This study enhances our understanding on the mechanism of regulation of aromatase expression by collagen and PGE2. Furthermore, this study provides a theoretical foundation for the development of specific inhibitors of aromatase by exploiting the signaling pathways identified herein in the context of @entity0 .
