Differential Expression of Wnt Genes in Normal and Flat Variants of PC 12 Cells, a Cell Line Responsive to Ectopic Wnt1 Expression

Abstract

Wnt genes encode secreted growth factor-like proteins that participate in growth regulation, differentiation and tumorigenesis. Ectopic expression of Wnt1 converts the PC 12 neural crest-derived rat pheochromocytoma cell line from a round phenotype that express chromaffin markers to flat adherent cells (termed PC12/Wnt1) that do not express them. A pool of spontaneously flat variants of PC 12 cells (PC12/flat) is phenotypically similar to the PC12/Wnt1 cells, but does not express Wnt1. Here we describe the expression of 13 Wnt genes in wild type PC 12, PC12/flat and PC12/Wnt1 cells. Wild type PC12 expressed Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt6, Wnt10a and Wnt11. Compared with expression in wild type cells, both PC12/flat and PC12/Wnt1 cells lost most or all expression of Wnt3a and Wnt4 and gained expression of Wnt7b, Wnt5a and Wnt6 expression was higher in PC12/Wnt1 cells than in PC 12 or PC12/flat. Wnt3 was expressed at low levels in both PC12 and PC12/flat, but was absent in PC12/Wnt1 cells. Wnt10a and Wnt11 were approximately equally expressed in the three groups, and Wnt2, Wnt5b, Wnt7a, Wnt10b and endogenous Wnt1 mRNAs were not detected. These results demonstrate that the expression of some Wnt genes changes in PC 12 cells upon conversion to the flat phenotype, and suggest that Wnt1 may modulate expression of several other Wnt genes in these cells.

Key Words:

• PC 12
• PC12/flat
• PC12/Wntl
• Wnt genes
• differentiation