HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium

Abstract

Summary HERG K + channels, besides contributing to regulate cardiac and neuronal excitability, are preferentially expressed in tumour cell lines of different histogenesis, where their role in the development and maintenance of the neoplastic phenotype is under study. We show here that both herg gene and HERG protein are expressed with high frequency in primary human endometrial cancers, as compared to normal and hyperplastic endometrium. RT-PCR and immunohistochemistry, using specific anti-HERG antibodies developed in our laboratory, were applied to tissue specimens obtained from 18 endometrial cancers and 11 non-cancerous endometrial tissues. herg RNA and HERG protein are expressed in 67% and 82%, respectively, of cancerous, while in only 18% of non-cancerous tissues. In particular, no expression was found in endometrial hyperplasia. Moreover, electrophysiological experiments confirmed the presence of functioning HERG channels on the plasma membrane of tumour cells. On the whole, these data are the first demonstration of the presence of HERG channels in primary human neoplasias, and could candidate HERG as a potential tool capable of marking cancerous versus hyperplastic endometrial growth.

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

“…Moreover, since the steady-state conductance of HERG channels is maximal around −30/−40 mV, I HERG appears to be particularly suitable to the clamping of V REST around these values in non-excitable cells, such as neoplastic or immature cells. Indeed, we showed that both herg and I HERG are preferentially expressed in tumor cell lines of different histogenesis, 28,29 in primary human endometrial cancers, 30 as well as in neuroblasts and myoblasts only at very early stages of embryo development, 31,32 and determine the V REST values in these cells. 28,29,33,34 Moreover, the human cell line FLG 29.1 derived from a patient with M5a type leukemia 35,36 expresses herg and a V REST which is governed by a unique K + current, namely I HERG , whose biophysical features keep this potential at strongly depolarized values.…”

“…Cells were homogenized in a guanidinium thiocyanate solution, and total RNA was extracted according to Cherubini et al 30 RNA purity and integrity was always checked by running an aliquot on a denaturing 1% agarose gel. 45 30 These primers encompass a nucleotide region from 2171 to 2746 of the human herg cDNA giving rise to a band 575 bp long. Thirty-five cycles of amplification were carried out after 2 min of enzyme activation at 94°C; denaturation was at 94°C for 30 s, annealing at 56°C for 1 min, and extention at 72°C for 1 min.…”

hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

“…The human ether a gò-gò related (hERG1) channels (KCNH2 or Kv 11.1, according to the most recent nomenclature) are voltagedependent K þ channels that are overexpressed in human endometrial adenocarcinoma (Cherubini et al, 2000), myeloid leukaemia (Pillozzi et al, 2002) and colorectal cancer (Lastraioli et al, 2004). In addition, they are often overexpressed in neoplastic cell lines of different origin.…”

HERG K+ channel related chemosensitivity to sparfloxacin in colon cancer cells

“…Recently, HERG has been found overexpressed in many human tumor cell lines and tumors of distinct histogenesis (6). Studies revealed that HERG protein is selectively upregulated in a variety of human and animal tumors while its expression is absent in the normal tissue or cell line counterparts (7,8). Moreover, selective pharmacological blockage of the HERG channel in several tumor cell types significantly reduced the cell proliferation (8)(9)(10).…”