Oncogenomics
Oncogene (2005) 24, 188–198. doi:10.1038/sj.onc.1207906
Loss of HOXC6 expression induces apoptosis in prostate cancer cells
Sumathi Ramachandran1,5, Pengbo Liu1,5, Andrew N Young1,2, Qiqin Yin-Goen1,2, So Dug Lim1, Noelani Laycock1, Mahul B Amin1,4, Jeffrey K Carney3, Fray F Marshall3,4, John A Petros1,2,3,4 and Carlos S Moreno1,4
- 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
- 2Atlanta VA Medical Center, Atlanta, GA, USA
- 3Department of Urology, Emory University School of Medicine, Atlanta, GA, USA
- 4Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
Correspondence: CS Moreno, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Dept. of Hematology & Oncology, Winship Cancer Institute, Whitehead Research Building, Rm 105J, 615 Michael St., Atlanta, GA 30322, USA. E-mail: cmoreno@emory.edu
5These authors contributed equally to this work
Received 30 January 2004; Revised 27 May 2004; Accepted 27 May 2004.
Abstract
We have performed whole genome expression profiling of 28 patient prostate tumor samples and 12 normal prostate samples and identified 55 upregulated and 60 downregulated genes significantly changed in prostate tumor samples compared to normal prostate tissues. Among the members of the upregulated gene set was the developmental transcription factor Homeobox C6 (HOXC6). Silencing of HOXC6 expression using small-interfering RNA (siRNA) resulted in decreased proliferation rates for both androgen-dependent LnCaP cells and the LnCaP-derived androgen-independent C4-2 cell line. Flow cytometry and immunoblotting for the caspase-cleaved form of poly-ADP ribose polymerase (PARP) determined that the decrease in cell numbers was due to increased apoptosis. To validate the specificity of the siRNA-induced apoptosis, LnCaP cells were cotransfected with siRNA specific to the HOXC6 3'UTR and a mammalian expression vector containing the HOXC6 open reading frame, but lacking the 3'UTR. Overexpression of HOXC6 rescued the LnCaP cells from HOXC6 siRNA-induced apoptosis, and increased growth of control GFP siRNA-transfected cells. Expression profiling of HOXC6 siRNA transfections and HOXC6 overexpression identified neutral endopeptidase (NEP) and insulin-like growth factor binding protein-3 (IGFBP-3) as potential proapoptotic repression targets of HOXC6. Our data suggest that HOXC6 may be a novel potential therapeutic target for prostate cancer.
Keywords:
prostate cancer, HOXC6, microarray, siRNA, apoptosis, IGFBP-3, NEP
