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Inhibition of Cell Growth by Nuclear Receptor COUP-TFI: Possible Involvement of Decorin in Growth Inhibition

Shinji Morii, Masaki Kato, Naohiko Seki, Natsuko Shinmen, Katsuro Iwase, Masaki Takiguchi and Takaki Hiwasa

The transcription factor, Chicken Ovalbumin Upstream Promoter-Transcription Factor I (COUP-TFI) is a member of the steroid/thyroid hormone receptor superfamily and plays important roles especially in development and differentiation. To investigate the effects of COUP-TFI on cell growth, we transfected this factor stably into Ha-rastransformed NIH3T3 (ras-NIH3T3) cells. Ectopic expression of COUP-TFI resulted in reduction of both proliferation rates and anchorage-independent growth. Flow cytometric analysis showed that progression through mid-S to G2/M phase was delayed in COUP-TFI transfectants. cDNA microarray analysis was performed to elucidate candidate genes whose expression levels were changed in response to COUP-TFI introduction. mRNA levels of decorin and cyclin G were elevated in COUP-TFI transfectants. Luciferase reporter assay revealed that the upstream promoter regions between –252 and -205 bp and between -204 and +42 bp of the decorin gene were responsible for COUPTFI. These suggest that decorin transactivated by COUP-TFI is one of the molecules which account for the growthinhibitory effects of COUP-TFI.