Profiling of retinoid mediated gene expression in synchronized human SCC cells using Atlas™ human cDNA expression arrays

✍ Scribed by Quan Le; Dianne Robert Soprano; Kenneth J. Soprano

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 448 KB
• Volume: 190
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.10051

✦ Synopsis

Abstract

While retinoids have been demonstrated to inhibit growth of many tumor cells, including SCC cells, the molecular mechanism by which retinoids suppress growth has not been elucidated. We previously found that the growth of SCC cells was significantly inhibited by all‐trans‐retinoic acid (all‐trans‐RA) treatment, and this inhibition was dependent on the binding and activation of RARs. These nuclear receptors bind retinoids and alter the rate of transcription of specific genes. To identify targets of the activated RARs which mediate growth inhibition, we growth arrested SCC‐25 cells in G‐0 and examined the effect of all‐trans‐RA on synchronized SCC‐25 cells. All‐trans‐RA inhibited G‐1 progression in quiescent SCC‐25 cells stimulated by FBS. More specifically, we found that the all‐trans‐RA execution point maps to mid/late G‐1, 6 to 10 h after stimulation. Using this synchronized cell system, we examined the expression of cell cycle regulatory genes in quiescent SCC‐25 cells stimulated with FBS and treated with all‐trans‐RA. We found few changes in expression of these genes which could account for all‐trans‐RA inhibition of SCC‐25 cell growth. In order to compare the patterns of expression of a wider selection of genes in all‐trans‐RA treated and non‐treated SCC‐25 cells, we have used expression array technology. We successfully performed expression profiling experiments on the Atlas™ Human cDNA arrays which contain 1176 human genes. We have identified several up‐regulated and several down‐regulated gene expression changes mediated by all‐trans‐RA treatment in synchronized SCC‐25 cells. This novel information will be useful in defining the mechanism by which retinoids suppress the growth of SCC cells. J. Cell. Physiol. 190: 345–355, 2002. © 2002 Wiley‐Liss, Inc.