Ets-1 activates overexpression of JunB and CD30 in Hodgkin's lymphoma and anaplastic large-cell lymphoma.

Overexpression of CD30 and JunB is a hallmark of tumor cells in Hodgkin's lymphoma (HL) and anaplastic large-cell lymphoma (ALCL). We reported that CD30-extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinase (MAPK) signaling induces JunB, which maintains constitutive activation of the CD30 promoter. Herein, we localize a cis-acting enhancer in the JunB promoter that is regulated by Ets-1. We show that E26 transformation-specific-1 (Ets-1) (-146 to -137) enhances JunB promoter activation in a manner that is dependent on CD30 or the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-ERK1/2 MAPK pathway. Ets-1 knockdown reduces the expression of both JunB and CD30, and CD30 knockdown significantly reduces JunB expression in HL and ALCL cell lines. NPM-ALK knockdown also reduces JunB expression in ALCL cell lines expressing NPM-ALK. Collectively, these results indicate that CD30 and NPM-ALK cooperate to activate the ERK1/2 MAPK-Ets-1 pathway. Ets-1, constitutively activated by ERK1/2-MAPK, plays a central role in the overexpression of JunB and CD30, which are both involved in the pathogenesis of HL and ALCL.

Watanabe M ，Itoh K ，Togano T ，Kadin ME ，Watanabe T ，Higashihara M ，Horie R ... -  《-》

JunB induced by constitutive CD30-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling activates the CD30 promoter in anaplastic large cell lymphoma and reed-sternberg cells of Hodgkin lymphoma.

Watanabe M ，Sasaki M ，Itoh K ，Higashihara M ，Umezawa K ，Kadin ME ，Abraham LJ ，Watanabe T ，Horie R ... -  《CANCER RESEARCH》

Hypomethylation of CD30 CpG islands with aberrant JunB expression drives CD30 induction in Hodgkin lymphoma and anaplastic large cell lymphoma.

Watanabe M ，Ogawa Y ，Itoh K ，Koiwa T ，Kadin ME ，Watanabe T ，Okayasu I ，Higashihara M ，Horie R ... -  《-》

The expression of CD30 in anaplastic large cell lymphoma is regulated by nucleophosmin-anaplastic lymphoma kinase-mediated JunB level in a cell type-specific manner.

Hsu FY ，Johnston PB ，Burke KA ，Zhao Y ... -  《CANCER RESEARCH》

The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling.

Staber PB ，Vesely P ，Haq N ，Ott RG ，Funato K ，Bambach I ，Fuchs C ，Schauer S ，Linkesch W ，Hrzenjak A ，Dirks WG ，Sexl V ，Bergler H ，Kadin ME ，Sternberg DW ，Kenner L ，Hoefler G ... -  《-》