Gene expression profiling of hedgehog pathway genes in epithelial cancers

Abstract

The Hedgehog (Hh) signaling pathway has been investigated in many cancer types and shown to have important effects, but not effectively studied in breast, colon and liver cancers. In this study, gene expression profile of BCL2, SHH, SMO, IHH, PTCH1, GLI1, GLI2 and GLI3 were analyzed in 15 breast, 14 colon, and 15 hepatocellular carcinoma (HCC) cell lines and 29 primary breast tumor samples and three matched normal tissue sample pools by quantitative real-time RT-PCR. Breast cell lines have different levels of target gene expression in the Hh pathway, such that this pathway is activated only in some of the breast carcinoma cell lines possibly through a ligand-independent pathway. In all the breast cancer cell lines studied, PTCH1, SMO, GLI3 and BCl2 had high expression. Expression profiles of the target genes predicted the estrogen receptor status correctly in 93% of the breast cell lines studied. In HCC cell lines, Hh pathway gene expression profile differentiates the poorly differentiated HCC cell lines from well differentiated ones in Discriminant Function Analysis (DFA) perfectly. High SMO and IHH expressions have been found to be markers for aberrant Hh pathway activity in the well differentiated HCC cell lines. In colon cancer cell lines deregulated expression profile among the genes were observed. In primary breast tumor samples, there was a very strong prediction for ER status of the samples with the expression of the genes included in this study. This is the first comprehensive study that shows the transcriptional gene expression profiles of the main target genes of the Hh pathway in cancer cell lines and breast cancer tissue samples