Faculty Collaboration Database

A preferential role for STAT5, not constitutively active STAT3, in promoting survival of a human lymphoid tumor. J Immunol 2006 Oct 15;177(8):5032-40

Date

10/04/2006

Pubmed ID

17015686

DOI

10.4049/jimmunol.177.8.5032

Scopus ID

2-s2.0-33749529310 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

STATs are believed to play key roles in normal and abnormal cell function. In the present work, we investigated the role of STATs in an IL-2-responsive human lymphoblastic lymphoma-derived cell line, YT. Only STAT3 was found constitutively tyrosine phosphorylated, but not other STATs. Hyperactive STAT3 was not attributable to a pre-existing intermediate affinity IL-2R complex and/or hyperactive Jak activity. Depletion of STAT3 protein expression reduced tumor cell viability with protracted kinetics (72-96 h), while TUNEL assays demonstrated cell death occurred via apoptosis. Interestingly, depletion of STAT5 in this same tumor induced more pronounced cell death compared with STAT3 depletion (24 h). Although IL-2 was able to rescue STAT3-depleted cells from death, it could not compensate for the loss of STAT5. To determine the prosurvival function of STAT3 vs STAT5 within the same tumor model, genes were profiled in STAT3- or STAT5-depleted YT cells by apoptosis-specific microarrays. Several differentially expressed genes were identified. Interestingly, those genes involved in NF-kappaB regulation, such as TNFR-associated factors 2 and 5 and B cell leukemia/lymphoma 10, were readily decreased upon STAT5, but not STAT3, depletion as validated by quantitative RT-PCR. These results suggest that STAT5 and, to a lesser extent, hyperactive STAT3 provide preferential and critical cell survival signals for certain human lymphoid tumors, indicating that nonhyperactive STATs should be considered as therapeutic targets for abrogating tumorigenesis.

Author List

Nagy ZS, Rui H, Stepkowski SM, Karras J, Kirken RA

MESH terms used to index this publication - Major topics in bold

Apoptosis
Cell Line, Tumor
Cell Survival
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Interleukin-2
NF-kappa B
Phosphorylation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
STAT3 Transcription Factor
STAT5 Transcription Factor