Comparative transcriptional study of the effects of high intracellular zinc on prostate carcinoma cells

Wong, P.F.; Abubakar, S. (2010) Comparative transcriptional study of the effects of high intracellular zinc on prostate carcinoma cells. Oncology reports, 23 (6). pp. 1501-16. ISSN 1791-2431

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Abstract

The normally high concentration of zinc in normal prostate gland is significantly reduced in malignant prostate tissues, but its precise role in prostate tumorigenesis remains unclear. The present study investigates the growth and transcriptional responses of LNCaP prostate cancer cells to prolonged high Zn2+ treatment. Restoration of high intracellular Zn2+ to LNCaP cells significantly reduced the cell proliferation rate by 42.2+/-7.4 at the exponential growth phase and the efficiency of colony formation on soft agar by 87.2+/-2.5 at week 5 post-treatment. At least 161 LNCaP cell genes responded to the high intracellular Zn2+, including approximately 10.6 genes that negatively regulate cell growth and approximately 16.1 genes that promote cancer cell proliferation. Inhibition of cell growth was transient as normal proliferation rate and colony formation efficiency were restored later even in the continuous presence of high intracellular Zn2+. RT-qPCR showed constitutively higher expression levels of FBL, CD164 and STEAP1 in LNCaP cells. FBL and CD164 were responsive to the treatment with Zn2+ in PNT2 prostate normal cells and were further overexpressed in the prolonged Zn2+-treated LNCaP cells. These observations suggest that in general high Zn2+ has suppressive effects on prostate cancer cell growth but continuous exposure to an environment of high Zn2+ can lead to the overexpression of cancer promoting genes such as FBL and CD164. This could be the antagonistic mechanism used to overcome the initial cell growth inhibitory effects of high Zn2+. These findings support a potential detrimental role of Zn2+ in prostate cancer.

Item Type: Article
Creators:
  1. Wong, P.F.
  2. Abubakar, S.(Department of Medical Microbiology, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, MALAYSIA)
Journal or Publication Title: Oncology reports
Additional Information: Wong, Pooi-Fong Abubakar, Sazaly eng Research Support, Non-U.S. Gov't Greece 2010/04/30 06:00 Oncol Rep. 2010 Jun;23(6):1501-16.
Uncontrolled Keywords: Cell Proliferation/drug effects Colony-Forming Units Assay Gene Expression Profiling Humans Male Oligonucleotide Array Sequence Analysis Prostatic Neoplasms/drug therapy/*metabolism RNA, Messenger/*genetics Reverse Transcriptase Polymerase Chain Reaction Trace Elements/*pharmacology Transcription, Genetic/*drug effects Tumor Cells, Cultured Tumor Markers, Biological/*genetics/metabolism Zinc/*pharmacology
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Mr Jenal S
Date Deposited: 12 Nov 2012 09:36
Last Modified: 12 Nov 2012 09:36
URI: http://eprints.um.edu.my/id/eprint/3945

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