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Cell Death Differ ; 19(11): 1826-35, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22705846

RESUMO

The tumor necrosis factor (TNF) family member APRIL (A proliferation inducing ligand) is a disease promoter in B-cell malignancies. APRIL has also been associated with a wide range of solid malignancies, including colorectal cancer (CRC). As evidence for a supportive role of APRIL in solid tumor formation was still lacking, we studied the involvement of APRIL in CRC. We observed that ectopic APRIL expression exacerbates the number and size of adenomas in Apc(Min) mice and in a mouse model for colitis-associated colon carcinogenesis. Furthermore, knockdown of APRIL in primary spheroid cultures of colon cancer cells and both mouse and human CRC cell lines reduced tumor clonogenicity and in vivo outgrowth. Taken together, our data therefore indicate that both tumor-derived APRIL and APRIL produced by non-tumor cells is supportive in colorectal tumorigenesis.


Assuntos
Transformação Celular Neoplásica , Neoplasias Colorretais/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Modelos Animais de Doenças , Humanos , Lentivirus/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos Transgênicos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Células Tumorais Cultivadas , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/antagonistas & inibidores , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
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