Heterogeneous Expressions of Apoptosis-related Genes in Development of Docetaxel-resistance of the PC3DR2 Prostate Cancer Cell Line

, Hakmin Lee; , Jin-Nyoung Ho; , Sang Chul Lee; , Jong Jin Oh; , Sung Kyu Hong; , Sang Eun Lee; , Seok-Soo Byun

Korean J Urol Oncol > Volume 12(2); 2014 > Article

Original Article

The Korean Journal of Urological Oncology 2014;12(2): 77-82.

PC3DR2 전립선암세포주의 Doxetaxel 내성 발현에서 세포고사관련 유전자의 이질적 발현

이학민, 호진녕, 이상철, 오종진, 홍성규, 이상은, 변석수

분당서울대학교병원 비뇨기과

Heterogeneous Expressions of Apoptosis-related Genes in Development of Docetaxel-resistance of the PC3DR2 Prostate Cancer Cell Line

Hakmin Lee , Jin-Nyoung Ho , Sang Chul Lee , Jong Jin Oh , Sung Kyu Hong , Sang Eun Lee , Seok-Soo Byun

Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea

Published online: August 30, 2014.

ABSTRACT

Purpose:
To understand the role of the apoptotic pathway of docetaxel- resistant human prostate cancer cell line (PC3DR2).
Materials and Methods:
PC3DR2 was established from the PC3 prostate cancer cell line by continuous exposure of escalating concentrations of docetaxel. Total RNA of PC3 and PC3DR2 were collected and cDNA microarray test was performed using GeneChip^Ⓡ Human Genome U133 Plus 2.0 Array. GenePlex^Ⓡ software was used for data analysis. Significantly different genes were identified with the cutoff 2.0 of fold change and p-value under 0.05 of Welch’s T-test. The apoptotic pathway heatmap was acquired to identify roles of apoptosis-related genes in development of docetaxel-resistance of PC3DR2.
Results:
There were 833 up-regulated and 908 down-regulated genes in the PC3DR2 compared to the control PC3. There were 72 significantly changed KEGG pathways in the PC3DR2 (cutoff: p＜0.05). There were 3 up-regulated (TRADD and 2 FLIPs) and 6 down-regulated (IAP, IKK, Bax, Akt/PKB, PKA and calcineurin) genes in the apoptotic pathway. These 9 changes led to 4 pro-apoptotic and 5 anti-apoptotic processes, indicating contradictory changes in the pathway.
Conclusions:
Heterogeneous expressions of apoptosis-related genes were identified in the development of docetaxel resistance of the PC3DR2. (Korean J Urol Oncol 2014;12:77-82)

Key Words: Prostate cancer; Drug resistance; cDNA microarray; Apoptosis