E74-like factor inhibition induces reacquisition of hormone sensitiveness decreasing period circadian protein homolog 1 expression in prostate cancer cells

Kohei Koyama, Kiyoshi Takahara, Teruo Inamoto, Naokazu Ibuki, Koichiro Minami, Hirofumi Uehara, Kazumasa Komura, Takeshi Nishida, Takeshi Sakamoto, Hajime Hirano, Hayahito Nomi, Satoshi Kiyama, Haruhito Azuma

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Abstract Purpose Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize. Methods In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent). Among them, we focused on a novel Ets transcription factor, E74-like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in comparison with LNCaP both in the microarray analysis and real-time polymerase chain reaction analysis, and investigated the biological role in acquisition of androgen-refractory PCa growth. Results Western blot analysis and morphological analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2 after ELF5 small interfering RNA transfection showed the same cell growth pattern of LNCaP. Conclusions Our in vitro experiments of cell growth and microarray analysis have demonstrated for the first time that decreased expression of period circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could be a novel potential target for the treatment of hormone-refractory PCa patients.

Original languageEnglish
Article number4
Pages (from-to)16-21
Number of pages6
JournalProstate International
Volume3
Issue number1
DOIs
Publication statusPublished - 01-01-2015
Externally publishedYes

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Period Circadian Proteins
Prostatic Neoplasms
Androgens
Hormones
Small Interfering RNA
Growth
Proto-Oncogene Proteins c-ets
Tissue Array Analysis
Co-Repressor Proteins
Androgen Receptors
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Fluorescence Microscopy
Confocal Microscopy
Cytosol
Transfection
Real-Time Polymerase Chain Reaction
Adenocarcinoma
Western Blotting
Cell Line

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Koyama, Kohei ; Takahara, Kiyoshi ; Inamoto, Teruo ; Ibuki, Naokazu ; Minami, Koichiro ; Uehara, Hirofumi ; Komura, Kazumasa ; Nishida, Takeshi ; Sakamoto, Takeshi ; Hirano, Hajime ; Nomi, Hayahito ; Kiyama, Satoshi ; Azuma, Haruhito. / E74-like factor inhibition induces reacquisition of hormone sensitiveness decreasing period circadian protein homolog 1 expression in prostate cancer cells. In: Prostate International. 2015 ; Vol. 3, No. 1. pp. 16-21.
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abstract = "Abstract Purpose Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize. Methods In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent). Among them, we focused on a novel Ets transcription factor, E74-like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in comparison with LNCaP both in the microarray analysis and real-time polymerase chain reaction analysis, and investigated the biological role in acquisition of androgen-refractory PCa growth. Results Western blot analysis and morphological analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2 after ELF5 small interfering RNA transfection showed the same cell growth pattern of LNCaP. Conclusions Our in vitro experiments of cell growth and microarray analysis have demonstrated for the first time that decreased expression of period circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could be a novel potential target for the treatment of hormone-refractory PCa patients.",
author = "Kohei Koyama and Kiyoshi Takahara and Teruo Inamoto and Naokazu Ibuki and Koichiro Minami and Hirofumi Uehara and Kazumasa Komura and Takeshi Nishida and Takeshi Sakamoto and Hajime Hirano and Hayahito Nomi and Satoshi Kiyama and Haruhito Azuma",
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Koyama, K, Takahara, K, Inamoto, T, Ibuki, N, Minami, K, Uehara, H, Komura, K, Nishida, T, Sakamoto, T, Hirano, H, Nomi, H, Kiyama, S & Azuma, H 2015, 'E74-like factor inhibition induces reacquisition of hormone sensitiveness decreasing period circadian protein homolog 1 expression in prostate cancer cells', Prostate International, vol. 3, no. 1, 4, pp. 16-21. https://doi.org/10.1016/j.prnil.2015.02.004

E74-like factor inhibition induces reacquisition of hormone sensitiveness decreasing period circadian protein homolog 1 expression in prostate cancer cells. / Koyama, Kohei; Takahara, Kiyoshi; Inamoto, Teruo; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Komura, Kazumasa; Nishida, Takeshi; Sakamoto, Takeshi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Azuma, Haruhito.

In: Prostate International, Vol. 3, No. 1, 4, 01.01.2015, p. 16-21.

Research output: Contribution to journalArticle

TY - JOUR

T1 - E74-like factor inhibition induces reacquisition of hormone sensitiveness decreasing period circadian protein homolog 1 expression in prostate cancer cells

AU - Koyama, Kohei

AU - Takahara, Kiyoshi

AU - Inamoto, Teruo

AU - Ibuki, Naokazu

AU - Minami, Koichiro

AU - Uehara, Hirofumi

AU - Komura, Kazumasa

AU - Nishida, Takeshi

AU - Sakamoto, Takeshi

AU - Hirano, Hajime

AU - Nomi, Hayahito

AU - Kiyama, Satoshi

AU - Azuma, Haruhito

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Abstract Purpose Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize. Methods In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent). Among them, we focused on a novel Ets transcription factor, E74-like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in comparison with LNCaP both in the microarray analysis and real-time polymerase chain reaction analysis, and investigated the biological role in acquisition of androgen-refractory PCa growth. Results Western blot analysis and morphological analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2 after ELF5 small interfering RNA transfection showed the same cell growth pattern of LNCaP. Conclusions Our in vitro experiments of cell growth and microarray analysis have demonstrated for the first time that decreased expression of period circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could be a novel potential target for the treatment of hormone-refractory PCa patients.

AB - Abstract Purpose Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize. Methods In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent). Among them, we focused on a novel Ets transcription factor, E74-like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in comparison with LNCaP both in the microarray analysis and real-time polymerase chain reaction analysis, and investigated the biological role in acquisition of androgen-refractory PCa growth. Results Western blot analysis and morphological analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2 after ELF5 small interfering RNA transfection showed the same cell growth pattern of LNCaP. Conclusions Our in vitro experiments of cell growth and microarray analysis have demonstrated for the first time that decreased expression of period circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could be a novel potential target for the treatment of hormone-refractory PCa patients.

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