Vitamin D3 modulated gene expression patterns in human primary normal and cancer prostate cells

✍ Scribed by Meral Guzey; Jianhua Luo; Robert H. Getzenberg

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 468 KB
• Volume: 93
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20182

✦ Synopsis

Abstract

The vitamin D receptor (VDR) is a member of the steroid/retinoid receptor superfamily of nuclear receptors and has potential tumor‐suppressive functions in prostate and other cancer types. Vitamin D~3~ (VD~3~) exerts its biological actions by binding within cells to VDR. The VDR then interacts with specific regions of the DNA in cells, and triggers changes in the activity of genes involved in cell division, cell survival, and cellular function. Using human primary cultures and the prostate cancer (PCa) cell line, ALVA‐31, we examined the effects of VD~3~ under different culture conditions. Complete G~0~/G~1~ arrest of ALVA‐31 cells and ∼50% inhibition of tumor stromal cell growth was observed. To determine changes in gene expression patterns related to VD~3~ activity, microarray analysis was performed. More than ∼20,000 genes were evaluated for twofold relative increases and decreases in expression levels. A number of the gene targets that were up‐ and down‐regulated are related to potential mechanisms of prostatic growth regulation. These include estrogen receptor (ER), heat shock proteins: 70 and 90, Apaf1, Her‐2/neu, and paxillin. Utilizing antibodies generated against these targets, we were able to confirm the changes at the protein level. These newly reported gene expression patterns provide novel information not only potential markers, but also on the genes involved in VD~3~ induced apoptosis in PCa. © 2004 Wiley‐Liss, Inc.