ZO-1 expression shows prognostic value in chronic B cell leukemia

Pavel P Nesmiyanov; Boris E Tolkachev; Andrey V Strygin

doi:10.1016/j.imbio.2015.08.008

ZO-1 expression shows prognostic value in chronic B cell leukemia

Immunobiology. 2016 Jan;221(1):6-11. doi: 10.1016/j.imbio.2015.08.008. Epub 2015 Aug 17.

Authors

Pavel P Nesmiyanov¹, Boris E Tolkachev², Andrey V Strygin³

Affiliations

¹ Fundamental Medicine and Biology Department, Volgograd State Medical University, Volgograd, Russia; Belozersky Research Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia. Electronic address: pavel.nesmiyanov@fulbrightmail.org.
² Fundamental Medicine and Biology Department, Volgograd State Medical University, Volgograd, Russia; Department of Hematology, Volgograd Regional Clinical Oncology Dispensary No.1, Volgograd, Russia.
³ Fundamental Medicine and Biology Department, Volgograd State Medical University, Volgograd, Russia; Volgograd Medical Science Center, Pharmacology Department, Laboratory for Genomics and Proteomics, Volgograd, Russia.

PMID: 26306999
DOI: 10.1016/j.imbio.2015.08.008

Abstract

Connexin-mediated gap junctions are vital for tumor cell function. Intracellular pathways of connexin signaling use Zonula Occludens protein-1 (ZO-1) as an intermediate. This report describes the ZO-1 and connexin 43 (Cx43) expression pattern in lymphocytes from chronic B-cell leukemia (B-CLL) patients. The ZO-1 and Cx43 expression in the B cells of 113 B-CLL patients was identified. Western blot and flow cytometry were used to determine protein expression. Results indicated that ZO-1 and Cx43 expression was reduced and correlated negatively with CD38 and Zap-70 expression. Inhibition of intercellular communication with anti-Cx43 antibodies, 1-octanol, or carbenoxolone resulted in induced cell apoptosis. These data suggest that ZO-1, along with CD38 and Zap-70, plays a role in cell cycle regulation in B-CLL and may be used as a prognostic marker in B-CLL monitoring.

Keywords: B-cell chronic leukemia; Connexin43; Gap junction intercellular communication; Prognosis; ZO-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

1-Octanol / pharmacology
ADP-ribosyl Cyclase 1 / genetics
ADP-ribosyl Cyclase 1 / metabolism
Adult
Aged
Antibodies / pharmacology
Apoptosis / drug effects
B-Lymphocytes / drug effects
B-Lymphocytes / metabolism*
B-Lymphocytes / pathology
Carbenoxolone / pharmacology
Cell Communication / drug effects
Cell Cycle / drug effects
Connexin 43 / antagonists & inhibitors
Connexin 43 / genetics*
Connexin 43 / metabolism
Female
Follow-Up Studies
Gene Expression Regulation, Leukemic*
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
Leukemia, Lymphocytic, Chronic, B-Cell / genetics
Leukemia, Lymphocytic, Chronic, B-Cell / mortality
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
Male
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism
Middle Aged
Primary Cell Culture
Prognosis
Signal Transduction
Survival Analysis
ZAP-70 Protein-Tyrosine Kinase / genetics
ZAP-70 Protein-Tyrosine Kinase / metabolism
Zonula Occludens-1 Protein / genetics*
Zonula Occludens-1 Protein / metabolism

Substances

Antibodies
Connexin 43
GJA1 protein, human
Membrane Glycoproteins
TJP1 protein, human
Zonula Occludens-1 Protein
ZAP-70 Protein-Tyrosine Kinase
CD38 protein, human
ADP-ribosyl Cyclase 1
Carbenoxolone
1-Octanol