Kwang Youl Lee" /> Kwang Youl Lee, Jeong Woon Lee, Hyun Jeong Nam, Jeong-Hyun Shim, Youngsup Song, and Keon Wook Kang*" /> Kwang Youl Lee, Jeong Woon Lee, Hyun Jeong Nam, Jeong-Hyun Shim, Youngsup Song, and Keon Wook Kang*. Mol. Cells 2011;32:107-11. https://doi.org/10.1007/s10059-011-0074-y">
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Mol. Cells 2011; 32(1): 107-111

Published online May 11, 2011

https://doi.org/10.1007/s10059-011-0074-y

© The Korean Society for Molecular and Cellular Biology

PI3-Kinase/p38 Kinase-Dependent E2F1 Activation Is Critical for Pin1 Induction in Tamoxifen-Resistant Breast Cancer Cells

Kwang Youl Lee1, Jeong Woon Lee, Hyun Jeong Nam, Jeong-Hyun Shim2, Youngsup Song3, and Keon Wook Kang*

Brain Korea 21 Project Team, College of Pharmacy, Chosun University, Gwangju 501-759, Korea,1College of Pharmacy, Chonnam National University, Gwangju 500-757, Korea, 2School of Medicine, Soonchunhyang University, Asan 336-745, Korea, 3The Salk Institute for Biological Studies, La Jolla, CA92037, USA

Correspondence to : *Correspondence: kwkang@chosun.ac.kr

Received: April 1, 2011; Accepted: April 19, 2011

Abstract

Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. We have shown that Pin1, a peptidyl prolyl isomerase, is consis-tently over-expressed in TAM-resistant MCF-7 cells (TAMR-MCF-7 cells) and plays a key role in the enhanced angiogenic potential of TAMR-MCF-7 cells. In the present study, we focused on signaling pathways for Pin1 up-regulation in TAMR-MCF-7 cells. Relative to MCF-7 cells, Pin1 gene transcription and E2 transcription factor1 (E2F1) expression were enhanced in TAMR-MCF-7 cells. E2F1 siRNA significantly reduced both the protein expression and the promoter transcriptional activity of Pin1. Activities of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK) and p38 kinase were all higher in TAMR-MCF-7 cells than in control MCF-7 cells and the enhanced Pin1 and E2F1 expression in TAMR-MCF-7 cells was reversed by inhibition of PI3K or p38 kinase. Moreover, the higher production of vascular endothelial growth factor (VEGF) in TAMR-MCF-7 cells was significantly diminished by suppression of PI3K or p38 kinase. These results suggest that Pin1 overexpression and subsequent VEGF production in TAMR-MCF-7 cells are mediated through PI3-kinase or p38 kinase-dependent E2F1 activation.

Keywords E2F1, p38 kinase, PI3-kinase, Pin1, tamoxifen-resistant breast cancer, VEGF

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Research Article

Mol. Cells 2011; 32(1): 107-111

Published online July 31, 2011 https://doi.org/10.1007/s10059-011-0074-y

Copyright © The Korean Society for Molecular and Cellular Biology.

PI3-Kinase/p38 Kinase-Dependent E2F1 Activation Is Critical for Pin1 Induction in Tamoxifen-Resistant Breast Cancer Cells

Kwang Youl Lee1, Jeong Woon Lee, Hyun Jeong Nam, Jeong-Hyun Shim2, Youngsup Song3, and Keon Wook Kang*

Brain Korea 21 Project Team, College of Pharmacy, Chosun University, Gwangju 501-759, Korea,1College of Pharmacy, Chonnam National University, Gwangju 500-757, Korea, 2School of Medicine, Soonchunhyang University, Asan 336-745, Korea, 3The Salk Institute for Biological Studies, La Jolla, CA92037, USA

Correspondence to:*Correspondence: kwkang@chosun.ac.kr

Received: April 1, 2011; Accepted: April 19, 2011

Abstract

Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. We have shown that Pin1, a peptidyl prolyl isomerase, is consis-tently over-expressed in TAM-resistant MCF-7 cells (TAMR-MCF-7 cells) and plays a key role in the enhanced angiogenic potential of TAMR-MCF-7 cells. In the present study, we focused on signaling pathways for Pin1 up-regulation in TAMR-MCF-7 cells. Relative to MCF-7 cells, Pin1 gene transcription and E2 transcription factor1 (E2F1) expression were enhanced in TAMR-MCF-7 cells. E2F1 siRNA significantly reduced both the protein expression and the promoter transcriptional activity of Pin1. Activities of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK) and p38 kinase were all higher in TAMR-MCF-7 cells than in control MCF-7 cells and the enhanced Pin1 and E2F1 expression in TAMR-MCF-7 cells was reversed by inhibition of PI3K or p38 kinase. Moreover, the higher production of vascular endothelial growth factor (VEGF) in TAMR-MCF-7 cells was significantly diminished by suppression of PI3K or p38 kinase. These results suggest that Pin1 overexpression and subsequent VEGF production in TAMR-MCF-7 cells are mediated through PI3-kinase or p38 kinase-dependent E2F1 activation.

Keywords: E2F1, p38 kinase, PI3-kinase, Pin1, tamoxifen-resistant breast cancer, VEGF

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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