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. 2009 Sep;175(3):1303–1314. doi: 10.2353/ajpath.2009.090163

Figure 5.

Figure 5

BMP signaling modulates Wif1 and Shh expression in cultured tumor cells and stimulates Wif1 promoter activity in HaCaT keratinocytes. A, B: The tumor cells were isolated and cultured with presence of 200 to 500 ng/ml BMP-4 or 200 ng/ml BMP-4 and 500 ng/ml Noggin. Cells were harvested 48 hours after treatment, and RNA and protein were isolated and processed for real-time PCR and Western blot analyses. Results show marked increase of Wif1 and decrease of Shh mRNAs (P < 0.05) and proteins after BMP-4 treatment. Effects of BMP-4 on the expression of the Wif1 and Shh transcripts are abrogated by Noggin (A). C: Effects of co-transfection with vectors containing constitutively active BMPR-IA (Alk3QD), BMPR-IB (Alk6QD), pCMVmSmad1, and/or pCMVSmad5 on transcription of the Wif1-Luc and Shh-Luc reporter plasmids containing human Wif1 and Shh promoter regions and pGVB2L-Luc (negative control). D: Scheme illustrating mechanisms of the effects of BMP signaling on distinct stages (initiation and progression) of tumor formation.