Loss of HOXC6 expression induces apoptosis in prostate cancer cells

Sumathi Ramachandran, Pengbo Liu, Andrew N. Young, Qiqin Yin-Goen, So Dug Lim, Noelani Laycock, Mahul Amin, Jeffrey K. Carney, Fray F. Marshall, John A. Petros, Carlos S. Moreno

Research output: Contribution to journalArticle

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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 down-regulated 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 siMNA specific to the HOXC6 3′UTM 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 siMNA-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.

Original languageEnglish (US)
Pages (from-to)188-198
Number of pages11
JournalOncogene
Volume24
Issue number1
DOIs
StatePublished - Jan 6 2005

Fingerprint

Homeobox Genes
Prostatic Neoplasms
Apoptosis
Small Interfering RNA
Prostate
neutral insulin
Androgens
Neprilysin
Insulin-Like Growth Factor Binding Protein 3
Poly(ADP-ribose) Polymerases
Caspases
Immunoblotting
Open Reading Frames
Genes
Transfection
Neoplasms
Flow Cytometry
Transcription Factors
Cell Count
Genome

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Ramachandran, S., Liu, P., Young, A. N., Yin-Goen, Q., Lim, S. D., Laycock, N., ... Moreno, C. S. (2005). Loss of HOXC6 expression induces apoptosis in prostate cancer cells. Oncogene, 24(1), 188-198. https://doi.org/10.1038/sj.onc.1207906

Loss of HOXC6 expression induces apoptosis in prostate cancer cells. / Ramachandran, Sumathi; Liu, Pengbo; Young, Andrew N.; Yin-Goen, Qiqin; Lim, So Dug; Laycock, Noelani; Amin, Mahul; Carney, Jeffrey K.; Marshall, Fray F.; Petros, John A.; Moreno, Carlos S.

In: Oncogene, Vol. 24, No. 1, 06.01.2005, p. 188-198.

Research output: Contribution to journalArticle

Ramachandran, S, Liu, P, Young, AN, Yin-Goen, Q, Lim, SD, Laycock, N, Amin, M, Carney, JK, Marshall, FF, Petros, JA & Moreno, CS 2005, 'Loss of HOXC6 expression induces apoptosis in prostate cancer cells', Oncogene, vol. 24, no. 1, pp. 188-198. https://doi.org/10.1038/sj.onc.1207906
Ramachandran S, Liu P, Young AN, Yin-Goen Q, Lim SD, Laycock N et al. Loss of HOXC6 expression induces apoptosis in prostate cancer cells. Oncogene. 2005 Jan 6;24(1):188-198. https://doi.org/10.1038/sj.onc.1207906
Ramachandran, Sumathi ; Liu, Pengbo ; Young, Andrew N. ; Yin-Goen, Qiqin ; Lim, So Dug ; Laycock, Noelani ; Amin, Mahul ; Carney, Jeffrey K. ; Marshall, Fray F. ; Petros, John A. ; Moreno, Carlos S. / Loss of HOXC6 expression induces apoptosis in prostate cancer cells. In: Oncogene. 2005 ; Vol. 24, No. 1. pp. 188-198.
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