Elsevier

European Journal of Cancer

Volume 37, Issue 16, November 2001, Pages 2129-2134
European Journal of Cancer

A novel gene on human chromosome 2p24 is differentially expressed between androgen-dependent and androgen-independent prostate cancer cells

https://doi.org/10.1016/S0959-8049(01)00259-3Get rights and content

Abstract

Identification of genes involved in the transition from androgen-dependent to androgen-independent prostate cancer is important to extend our current knowledge of the disease. Using differential display RT-PCR analysis between androgen-dependent and androgen-independent prostate cancer cells, we have identified a novel gene, designated GC109. GC109 harbours a putative Cys-His cluster, a nuclear localisation signal, a leucine zipper and a ret finger protein (rfp)-like domain. GC109 mRNA expression in normal human tissues was found not to be restricted to the prostate. However, using a variety of 15 human cancer cell lines, GC109 mRNA was preferentially expressed in androgen-dependent LNCaP-FGC, compared with androgen-independent LNCaP-LNO, DU145 and PC3 human prostate cancer cells. Finally, the GC109 gene was mapped on human chromosome 2p24. Based on its protein domain structure and chromosomal localisation, we hypothesise that GC109 may be involved in chromosomal rearrangements in prostate cancer.

Introduction

Prostate cancer is the second leading cause of male cancer-related deaths and the most commonly diagnosed cancer in elderly men in the Western world [1]. Prostate cancer is initially an androgen-dependent disease and can be treated effectively by inhibiting endogenous androgen production or action. However, it has been reported that in an animal model, almost all prostate tumours will progress, which results in growth of androgen-independent cells and subsequent development of hormone-refractory prostate disease. The mechanism of prostate cancer progression from an androgen-dependent to an androgen-independent state is not fully understood [2]. Genetic alterations (loss and gain) most likely play a role during prostate cancer progression. It has been reported that major genetic alterations occur during androgen-dependent prostate cancer growth, and minor genetic alterations occur during androgen-independent prostate cancer growth 3, 4. Identification of genetic factors that are differentially expressed between androgen-dependent and androgen-independent prostate cancer may be important to extend our current knowledge of the molecular mechanism(s) underlying the development of hormone-refractory prostate cancer.

Applying differential display reverse transcriptase-polymerase chain reaction (RT-PCR) analysis to androgen-dependent and androgen-independent prostate cancer cells, we have identified and cloned several cDNA transcripts 5, 6, 7. Here, we report on the identification of a novel gene, designated GC109. GC109 is localised on the human chromosome 2p24 locus and was found to be expressed more highly in androgen-dependent compared with androgen-independent prostate cancer cell lines.

Section snippets

Human cancer cell lines

The lymph node carcinoma of the prostate-fast growing colony (LNCaP-FGC) and lymph node carcinoma of the prostate-lymph node original (LNCaP-LNO) cell lines [8] were gifts from Dr J.S. Horoszewicz (Buffalo, NY, USA) and were propagated as described in 5, 9.

The human cancer cell lines PC3 and DU145 (androgen-independent prostate carcinomas), ZR-75-1 (oestrogen-dependent breast carcinoma), T47D and MCF7 (oestrogen-responsive breast carcinomas), MDA-MB-231 and SKBR-3 (oestrogen-independent breast

GC109 is differentially expressed between LNCaP-FGC and LNCaP-LNO cells

Two genetically related LNCaP cell lines were used to isolate genes involved in androgen-independent prostate cancer development. The LNCaP-FGC cell line is androgen-dependent and has an optimal growth rate at 10−10 M R1881 (synthetic androgen), whereas higher concentrations did not stimulate growth at all. Both 10−7 M 1.25 (OH)2D3 (vitamin D3) or a combination of 10−8 M R1881 plus 10−7 M 1.25 (OH)2D3 did not stimulate growth (data not shown). The LNCaP-LNO cell line is androgen-independent and

Discussion

Using differential display RT-PCR analysis and a controlled cell culture system, GC109 was identified (Fig. 1). GC109 mRNA is higher expressed in androgen-dependent LNCaP-FGC compared with androgen-independent LNCaP-LNO prostate cancer cells. In normal human tissues, GC109 mRNA expression was not limited to the prostate, but was also observed in various other human tissues (Fig. 2). In fetal tissues, expression was in general lower compared with their normal human counterparts, except for fetal

Acknowledgments

This work was sponsored by the Dutch Cancer Society (KWF/NKB) (grant no. EUR 95-1031).

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