Gene expression profiling of hedgehog pathway genes in epithelial cancers
Author
Öztürk, Özlem Akıllı
Advisor
Yuluğ, Işık G.
Date
2006Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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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