RNAi silencing of the WT1 gene inhibits cell proliferation and induces apoptosis in the B16F10 murine melanoma cell line.
The Wilms' tumor protein 1 (WT1) is essential for tumor cell proliferation and is highly expressed in various hematological and solid malignancies including human malignant melanoma. We investigated whether WT1 expression is essential for growth in the B16F10 murine melanoma cell line. Toward this end, we examined WT1 protein expression and WT1 isoforms (17AA+/17AA-, KTS+/KTS-) in this cell line. WT1 was silenced by two RNA interference constructs, designated WT1-1 and WT1-2. RNA interference-mediated reduction of WT1 protein expression significantly inhibited B16F10 cell viability. Loss of WT1 also increased caspase-3 and poly-ADP-ribose polymerase activation, as well as apoptotic body formation, chromatin condensation, and DNA fragmentation. Together, these findings implicate decreased WT1 protein levels in the induction of apoptosis. These results imply that WT1 plays a distinct role in B16F10 melanoma growth.
Zamora-Avila
Diana E
DE
Immunology and Virology Department, Biological Sciences Faculty, University Autónoma of Nuevo Leon, Nicolás de los Garza, Nuevo León, México.
Franco-Molina
Moisés A
MA
Trejo-Avila
Laura M
LM
Rodríguez-Padilla
Cristina
C
Reséndez-Pérez
Diana
D
Zapata-Benavides
Pablo
P
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D016162:Genes, Wilms Tumor; D006801:Humans; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D025721:WT1 Proteins; C505409:Casp3 protein, mouse; D053148:Caspase 3