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CD73 participates in cellular multiresistance program and protects against TRAIL-induced apoptosis.


ABSTRACT: The molecular mechanisms underlying the multiresistant phenotype of leukemic and other cancer cells are incompletely understood. We used expression arrays to reveal differences in the gene expression profiles of an apoptosis-resistant T cell leukemia clone (A4) and normally apoptosis-sensitive parental Jurkat cells. CD73 (ecto-5'-nucleotidase) was the most up-regulated gene in the resistant A4 cell clone. A4 cells displayed CD73 surface expression and significant ecto-5'-nucleotidase activity. The role of CD73 was confirmed by transfection of wild-type CD73 into native Jurkat cells, which led to specific resistance against TRAIL-induced apoptosis, but not other types of apoptosis. The protective role of CD73 was further confirmed by small interfering RNA-mediated down-regulation of CD73, restoring TRAIL sensitivity. CD73-mediated resistance was independent of enzymatic activity of CD73, but was reliant on the anchoring of the protein to the membrane via GPI. We suggest that the inhibition of TRAIL signaling works through interaction of CD73 with death receptor 5, as CD73 and death receptor 5 could be coimmunoprecipitated and were shown to be colocalized in the plasma membrane by confocal microscopy. We propose that CD73 is a component of multiresistance machinery, the transcription of which is activated under selective pressure of the immune system.

SUBMITTER: Mikhailov A 

PROVIDER: S-EPMC5584620 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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CD73 participates in cellular multiresistance program and protects against TRAIL-induced apoptosis.

Mikhailov Andrey A   Sokolovskaya Alice A   Yegutkin Gennady G GG   Amdahl Hanne H   West Anne A   Yagita Hideo H   Lahesmaa Riitta R   Thompson Linda F LF   Jalkanen Sirpa S   Blokhin Dmitry D   Eriksson John E JE  

Journal of immunology (Baltimore, Md. : 1950) 20080701 1


The molecular mechanisms underlying the multiresistant phenotype of leukemic and other cancer cells are incompletely understood. We used expression arrays to reveal differences in the gene expression profiles of an apoptosis-resistant T cell leukemia clone (A4) and normally apoptosis-sensitive parental Jurkat cells. CD73 (ecto-5'-nucleotidase) was the most up-regulated gene in the resistant A4 cell clone. A4 cells displayed CD73 surface expression and significant ecto-5'-nucleotidase activity. T  ...[more]

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