Expression of transforming growth factor β1 promotes cholangiocarcinoma development and progression.

ABSTRACT:

Background and aims

The role of transforming growth factor beta 1 (TGFβ1) in cholangiocarcinoma (CCA) initiation and growth requires further definition.

Methods

We employed pharmacological and genetic approaches to inhibit or enhance TGFβ1 signaling, respectively, and determine the cellular mechanisms involved.

Results

It was observed that inhibiting TGFβ1 activity with short hairpin RNA (shRNA) or pharmaceutical agents suppressed CCA development and growth, whereas overexpression of TGFβ1 enhanced CCA tumor size and promoted intrahepatic metastasis in a rat model. Suppression of TGFβ1 activity inhibits downstream target gene expression mediated by miR-34a that includes cyclin D1, CDK6, and c-Met. In addition, "knockdown" of TGFβ1 expression revealed a miR-34a positiv

SUBMITTER: Huang CK 

PROVIDER: S-EPMC4973469 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature