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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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-a36 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.

Original languageEnglish
Pages (from-to)21328-21340
Number of pages13
JournalOncotarget
Volume6
Issue number25
DOIs
Publication statusPublished - 2015 Jan 1

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Estrogens
Carcinogenesis
Endometrial Neoplasms
ras Proteins
Heterografts
Neoplasms
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Koo, Kyoung Hwa ; Jeong, Woo Jeong ; Cho, Yong Hee ; Park, Jong Chan ; Min, Do Sik ; Choi, Kang-Yell. / K-Ras stabilization by estrogen via PKCδ is involved in endometrial tumorigenesis. In: Oncotarget. 2015 ; Vol. 6, No. 25. pp. 21328-21340.
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K-Ras stabilization by estrogen via PKCδ is involved in endometrial tumorigenesis. / Koo, Kyoung Hwa; Jeong, Woo Jeong; Cho, Yong Hee; Park, Jong Chan; Min, Do Sik; Choi, Kang-Yell.

In: Oncotarget, Vol. 6, No. 25, 01.01.2015, p. 21328-21340.

Research output: Contribution to journalArticle

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