Vitamin D3 modulated gene expression patterns in human primary normal and cancer prostate cells.
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 D3 (VD3) 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 VD3 under different culture conditions. Complete G0/G1 arrest of ALVA-31 cells and approximately 50% inhibition of tumor stromal cell growth was observed. To determine changes in gene expression patterns related to VD3 activity, microarray analysis was performed. More than approximately 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 VD3 induced apoptosis in PCa.
Guzey
Meral
M
Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania 15232, USA.
Luo
Jianhua
J
Getzenberg
Robert H
RH
D053477:Apoptotic Protease-Activating Factor 1; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D053477:Apoptotic Protease-Activating Factor 1; D002762:Cholecalciferol; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D006360:Heat-Shock Proteins; D051419:Paxillin; D010750:Phosphoproteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; C506592:APAF1 protein, human; C496061:PXN protein, human