Microarray Technology Used to Identify Altered Expression of Thirty Genes in Response to GLI1 Expression

Phil Iannaccone, MD
Northwestern University Medical School
ES10549

Background: The protein GLI1 is a member of the family of zinc finger transcription factors. The GLI family mediates the expression of Sonic hedgehog, an intercellular signaling molecule, and is critical in regulating cell cycle and differentiation in mammalian development. GLI1 transforms cells in culture and is also expressed in several human cancers such as basal cell carcinoma, sarcomas, and medulloblastomas, which account for 20% of childhood brain tumors.

To identify genes specific to the GLI1 transformation process, these investigators examined the expression profiles of cells transformed with GLI1 and compared them to profiles from cells transformed with Ha-ras in a cell line. Microarray technology was used for these comparisons because it allows for the study of the expression of thousands of genes in a single experiment.

Advance: The profiling experiments identified 30 genes that were altered by GLI1 expression. In the Ha-ras transformed cells, 124 genes were changed. Seven genes had altered expression levels in both types of transformed cells. GLI1 expression altered the expression of genes involved in cell cycle control, cell adhesion, signal transduction, and the regulation of apoptosis or programmed cell death. Many of the GLI1 targets identified in this study increase cell proliferation which indicates that GLI1-induced cell transformation occurs through multiple targets.

Implication: The number and breadth of function of the genes whose expression was altered by GLI1 demonstrates its importance as an important player in the control of normal developmental processes as well as the development of a variety of cancers. The cascade of events resulting from GLI1 expression provides many opportunities for further research and possible sites of attack for new cancer therapies.

Citation: Yoon JW, Kita Y, Frank DJ, Majewski RR, Konicek BA, Nobrega MA, Jacob H, Walterhouse D, Iannaccone P. Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. J Biol Chem. 2002 Feb 15;277(7):5548-55.