Details

Autor(en) / Beteiligte

• Watanabe, Mariko
• Itoh, Kinji
• Togano, Tomiteru
• Kadin, Marshall E
• Watanabe, Toshiki
• Higashihara, Masaaki
• Horie, Ryouichi

Titel

Ets-1 Activates Overexpression of JunB and CD30 in Hodgkin's Lymphoma and Anaplastic Large-Cell Lymphoma

Ist Teil von

• The American journal of pathology, 2012-02, Vol.180 (2), p.831-838

Ort / Verlag

Bethesda, MD: Elsevier Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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.