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IL-6 promotes MYC-induced B cell lymphomagenesis independent of STAT3.


ABSTRACT: The inflammatory cytokine IL-6 is known to play a causal role in the promotion of cancer, although the underlying mechanisms remain to be completely understood. Interplay between endogenous and environmental cues determines the fate of cancer development. The E?-myc transgenic mouse expresses elevated levels of c-Myc in the B cell lineage and develops B cell lymphomas with associated mutations in p53 or other genes linked to apoptosis. We generated E?-myc mice that either lacked the IL-6 gene, or lacked the STAT3 gene specifically in B cells to determine the role of the IL-6/JAK/STAT3 pathway in tumor development. Using the E?-myc lymphoma mouse model, we demonstrate that IL-6 is a critical tumor promoter during early stages of B cell lymphomagenesis. IL-6 is shown to inhibit the expression of tumor suppressors, notably BIM and PTEN, and this may contribute to advancing MYC-driven B cell tumorigenesis. Several miRNAs known to target BIM and PTEN are upregulated by IL-6 and likely lead to the stable suppression of pro-apoptotic pathways early during the tumorigenic process. STAT3, a classical downstream effector of IL-6, appears dispensable for E?-myc driven lymphomagenesis. We conclude that the growth-promoting and anti-apoptotic mechanisms activated by IL-6 are critically involved in E?-myc driven tumor initiation and progression, but the B cell intrinsic expression of STAT3 is not required.

SUBMITTER: Petrenko O 

PROVIDER: S-EPMC7924759 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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IL-6 promotes MYC-induced B cell lymphomagenesis independent of STAT3.

Petrenko Oleksi O   Li Jinyu J   Cimica Velasco V   Mena-Taboada Patricio P   Shin Ha Youn HY   D'Amico Stephen S   Reich Nancy C NC  

PloS one 20210302 3


The inflammatory cytokine IL-6 is known to play a causal role in the promotion of cancer, although the underlying mechanisms remain to be completely understood. Interplay between endogenous and environmental cues determines the fate of cancer development. The Eμ-myc transgenic mouse expresses elevated levels of c-Myc in the B cell lineage and develops B cell lymphomas with associated mutations in p53 or other genes linked to apoptosis. We generated Eμ-myc mice that either lacked the IL-6 gene, o  ...[more]

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