K-Ras stabilization by estrogen via PKCδ is involved in endometrial tumorigenesis

Kyoung-Hwa Koo; Woo-Jeong Jeong; Yong-Hee Cho; Jong-Chan Park; Do Sik Min; Kang-Yell Choi

doi:10.18632/oncotarget.4049

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Learn about our FREE

Post-Publication Promotion Services

50% on all publication fees until the end of 2024.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

K-Ras stabilization by estrogen via PKCδ is involved in endometrial tumorigenesis

Kyoung-Hwa Koo, Woo-Jeong Jeong, Yong-Hee Cho, Jong-Chan Park, Do Sik Min and Kang-Yell Choi _

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2015; 6:21328-21340. https://doi.org/10.18632/oncotarget.4049

Metrics: PDF 2013 views | HTML 2852 views | ?

Abstract

Kyoung-Hwa Koo1,2, Woo-Jeong Jeong1,2, Yong-Hee Cho1,2, Jong-Chan Park1,2, Do Sik Min1,3 and Kang-Yell Choi1,2

1 Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea

2 Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea

3 Department of Molecular Biology, College of Natural Science, Pusan National University, Pusan, Korea

Correspondence to:

Kang-Yell Choi, email:

Keywords: endometrial cancer, estrogen, tumorigenesis, K-Ras, PKCδ

Received: February 27, 2015 Accepted: April 30, 2015 Published: May 08, 2015

Abstract

Estrogens are considered as a major risk factor of endometrial cancer. In this study, we identified a mechanism of tumorigenesis in which K-Ras protein is stabilized via estrogen signaling through the ER-α36 receptor. PKCδ was shown to stabilize K-Ras specifically via estrogen signaling. Estrogens stabilize K-Ras via inhibition of polyubiquitylation-dependent proteasomal degradation. Estrogen-induced cellular transformation was abolished by either K-Ras or PKCδ knockdown. The role of PKCδ in estrogen-induced tumorigenesis was confirmed in a mouse xenograft model by reduction of tumors after treatment with rottlerin, a PKCδ inhibitor. Finally, levels of PKCδ correlated with that of Ras in human endometrial tumor tissues. Stabilization of K-Ras by estrogen signaling involving PKCδ up-regulation provides a potential therapeutic approach for treatment of endometrial cancer.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 4049

Publication Alerts

Post-Publication Promotion

Publication Discount

Research Papers:

K-Ras stabilization by estrogen via PKCδ is involved in endometrial tumorigenesis

Abstract