Immunohistochemical detection of tankyrase 2 in human breast tumors and normal renal tissue

Abstract

Tankyrase, which functions at telomeres and other cellular compartments, is thought to be a positive regulator of telomerase; its isoenzyme tankyrase 2 has been cloned as a putative cancer antigen. This pilot immunohistochemical study was designed to examine whether tumors overexpress tankyrase 2. An antibody was generated by using synthetic peptide specific for tankyrase 2 and was tested by Western blot and immunocytochemically; no cross-reaction with isoenzyme 1 was revealed. Among tissue sections, two tumors of 18 specimens were positive for tankyrase 2. Others were negative or contained barely detectable protein. The surrounding normal tissues were negative. Tankyrase 2 was also revealed in epithelial cells of a limited number of normal renal tubules, whereas other renal tissues were negative. These data suggest that tankyrase 2 is not expressed ubiquitously in human tissues. To determine whether the up-regulation of tankyrase 2 is associated with tissue regeneration and cell proliferation, we compared the activity and concentration of the enzyme in a model human embryonic kidney cell line 293 arrested by serum deprivation and restimulated with serum. The serum-starved quiescent cell culture exhibited detectable protein as did the proliferating cells; enzyme activity dramatically increased in the latter. We conclude that pathologic overexpression of tankyrase 2 in some tumors may be a result of the cancer-related adaptation of the malignant cells dependent on tankyrase activity. Under normal conditions, the protein might be up-regulated during cell differentiation and also posttranslationally in proliferating cells.

RDX Induces Aberrant Expression of MicroRNAs in Mouse Brain and Liver

“…Binding of TRF1 to the telomere can be inhibited by ADP ribosylation of TRF1 by TNKS-1 and TNKS-2 (Cook et al 2002; Smith et al 1998). Aberrant expression of TNKS has been found in cancers and neoplasms, including multiple myeloma, plasma cell leukemia (Xu et al 2001), bladder and colon cancer (Shebzukhov et al 2008), and breast cancer (Sidorova et al 2006). Knockdown of TNKS-1 by small interfering RNA blocked mitosis due to sister chromatids remaining associated in telomeres (Dynek and Smith 2004).…”

Frameshift mutations of poly(adenosine diphosphate-ribose) polymerase genes in gastric and colorectal cancers with microsatellite instability

“…The 2 tankyrases bind and poly(ADP-ribosyl)ate axin protein in the β-catenin complex and regulate the Wnt signaling [32]. In addition, both tankyrases are expressed in normal and cancer tissues of colon, suggesting a possibility that they might play roles in them [33,34]. Frameshift mutations of PARP14, TNKS, and TNKS2 genes in the cancers with MSI-H would result in production of truncated proteins and alter their functions in the cancer cells.…”

Determining and Interpreting New Predictive Rules for Breast Cancer Familial Inheritance

“…Another gene located in this locus, TANK, is linked to telomerase. Tankyrase, a positive regulator of telomerase activity, has been reported to be upregulated in breast cancers (Sidorova et al, 2006).…”