herg1 Gene and HERG1 Protein Are Overexpressed in Colorectal Cancers and Regulate Cell Invasion of Tumor Cells

Abstract

The acquisition of the capacity to invade surrounding tissues confers a more malignant phenotype to tumor cells and is necessary for the establishment of metastases. The understanding of the molecular mechanisms underlying cell invasion in human solid tumors such as colorectal cancers could provide not only more sensitive prognostic analyses but also novel molecular targets for cancer therapy.We report in this article that K ؉ ion channels belonging to the HERG family are important determinants for the acquisition of an invasive phenotype in colorectal cancers. The herg1 gene and HERG1 protein are expressed in many colon cancer cell lines, and the activity of HERG channels modulates colon cancer cell invasiveness. Moreover, the amount of HERG1 protein expressed on the plasma membrane is directly related to the invasive phenotype of colon cancer cells.Finally, both the herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers, whereas no expression could be detected either in normal colonic mucosa or in adenomas.

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

“…The I hERG activation curve was obtained from peak tail currents at À120 mV, elicited after 3 s conditioning steps from À60 to (Lastraioli et al, 2004). Whole-cell currents were studied by using a two-step protocol (Hofmann et al, 2001).…”

“…Antigen retrieval and staining conditions were the same as those reported in Lastraioli et al (2004). hERG1 immunochemical detection was carried out using commercially available kits (PicTure Plus kit, Zymed Laboratories, CA, USA).…”

“…The detection of hERG1 channel by protein extraction and Western blotting was performed as reported in Lastraioli et al (2004). For testing VEGF secretion, cells were seeded into 24-well cell clusters at 3 Â 10 5 cells per well in Opti-Mem (Invitrogen).…”

“…The antibodies had been previously tested in human colorectal cancers (Lastraioli et al, 2004). Representative photographs are shown in Figure 5.…”

“…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.…”