DNA primase polypeptide 1 (PRIM1) involves in estrogen-induced breast cancer formation through activation of the G2/M cell cycle checkpoint

Wei-Hwa Lee, Li-Ching Chen, Chia-Jung Lee, Chi-Cheng Huang, Yuan-Soon Ho, Po-Sheng Yang, Chi-Tang Ho, Hang-Lung Chang, I-Hsuan Lin, Hui-Wen Chang, Yun-Ru Liu, Chih-Hsiung Wu, Shih-Hsin Tu

研究成果: 雜誌貢獻文章

2 引文 (Scopus)

摘要

The DNA primase polypeptide 1 (PRIM1) is responsible for synthesizing small RNA primers for Okazaki fragments generated during discontinuous DNA replication. PRIM1 mRNA expression levels in breast tumor samples were detected by real-time PCR analysis. Xenografted tumor model was established to study the carcinogenic role of PRIM1 and its potential therapeutic applications. The average PRIM1 mRNA (copy number × 10 3/μg) expression was 4.7-fold higher in tumors than in normal tissue (*p = 0.005, n = 254). PRIM1 was detected preferentially at a higher level (>40-fold) in poorly differentiated tumor tissues (n = 46) compared with more highly differentiated tumors tissues (n = 10) (*p = 0.005). Poor overall survival rate was correlated to the estrogen receptor positive (ER+, n = 20) patients with higher PRIM1 expression when compare to the ER− (n = 10) patients (Chi Square test, p = 0.03). Stable expression of PRIM1-siRNA in the ER+ BT-474 cells-xenograft tumors significantly reduced tumor volume in SCID mice (*p = 0.005). The anti-tumoral effects of inotilone isolated from Phellinus linteus was tested and had significant effects on the inhibition of PRIM1 protein expression in ER+ breast cancer cells. In vivo study was performed by administering inotilone (10 mg/kg, twice a week for 6 weeks), which resulted in significantly reduced BT-474-xenografted tumor growth volume compared with control (n =5 per group, *p < 0.05). This study provides evidences for the prognostic effects of PRIM1 with poor overall survival rate in the ER+ patients and will be valuable to test for therapeutic purpose.

原文英語
頁(從 - 到)615-630
頁數16
期刊International Journal of Cancer
144
發行號3
DOIs
出版狀態已發佈 - 二月 1 2019

指紋

DNA Primase
G2 Phase Cell Cycle Checkpoints
Estrogens
Breast Neoplasms
Peptides
Neoplasms
Tumor Burden
Survival Rate
Messenger RNA
SCID Mice
Chi-Square Distribution
DNA Replication
Heterografts
Estrogen Receptors
Small Interfering RNA
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

DNA primase polypeptide 1 (PRIM1) involves in estrogen-induced breast cancer formation through activation of the G2/M cell cycle checkpoint. / Lee, Wei-Hwa; Chen, Li-Ching; Lee, Chia-Jung; Huang, Chi-Cheng; Ho, Yuan-Soon; Yang, Po-Sheng; Ho, Chi-Tang; Chang, Hang-Lung; Lin, I-Hsuan; Chang, Hui-Wen; Liu, Yun-Ru; Wu, Chih-Hsiung; Tu, Shih-Hsin.

於: International Journal of Cancer, 卷 144, 編號 3, 01.02.2019, p. 615-630.

研究成果: 雜誌貢獻文章

Lee, Wei-Hwa ; Chen, Li-Ching ; Lee, Chia-Jung ; Huang, Chi-Cheng ; Ho, Yuan-Soon ; Yang, Po-Sheng ; Ho, Chi-Tang ; Chang, Hang-Lung ; Lin, I-Hsuan ; Chang, Hui-Wen ; Liu, Yun-Ru ; Wu, Chih-Hsiung ; Tu, Shih-Hsin. / DNA primase polypeptide 1 (PRIM1) involves in estrogen-induced breast cancer formation through activation of the G2/M cell cycle checkpoint. 於: International Journal of Cancer. 2019 ; 卷 144, 編號 3. 頁 615-630.
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abstract = "The DNA primase polypeptide 1 (PRIM1) is responsible for synthesizing small RNA primers for Okazaki fragments generated during discontinuous DNA replication. PRIM1 mRNA expression levels in breast tumor samples were detected by real-time PCR analysis. Xenografted tumor model was established to study the carcinogenic role of PRIM1 and its potential therapeutic applications. The average PRIM1 mRNA (copy number × 10 3/μg) expression was 4.7-fold higher in tumors than in normal tissue (*p = 0.005, n = 254). PRIM1 was detected preferentially at a higher level (>40-fold) in poorly differentiated tumor tissues (n = 46) compared with more highly differentiated tumors tissues (n = 10) (*p = 0.005). Poor overall survival rate was correlated to the estrogen receptor positive (ER+, n = 20) patients with higher PRIM1 expression when compare to the ER− (n = 10) patients (Chi Square test, p = 0.03). Stable expression of PRIM1-siRNA in the ER+ BT-474 cells-xenograft tumors significantly reduced tumor volume in SCID mice (*p = 0.005). The anti-tumoral effects of inotilone isolated from Phellinus linteus was tested and had significant effects on the inhibition of PRIM1 protein expression in ER+ breast cancer cells. In vivo study was performed by administering inotilone (10 mg/kg, twice a week for 6 weeks), which resulted in significantly reduced BT-474-xenografted tumor growth volume compared with control (n =5 per group, *p < 0.05). This study provides evidences for the prognostic effects of PRIM1 with poor overall survival rate in the ER+ patients and will be valuable to test for therapeutic purpose.",
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AU - Huang, Chi-Cheng

AU - Ho, Yuan-Soon

AU - Yang, Po-Sheng

AU - Ho, Chi-Tang

AU - Chang, Hang-Lung

AU - Lin, I-Hsuan

AU - Chang, Hui-Wen

AU - Liu, Yun-Ru

AU - Wu, Chih-Hsiung

AU - Tu, Shih-Hsin

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