Tumorigenicity of human breast cancer is associated with loss of the Ca2+-activated chloride channel CLCA2.
The human Ca2+-activated chloride channel-2 (CLCA2) is expressed in normal breast epithelium but not in breast tumors of different stages of progression. Northern analysis of nontransformed and transformed breast epithelial cell lines revealed CLCA2 expression in the nontransformed cell line MCF10A and the nontumorigenic cell line MDA-MB-453, whereas all tumorigenic cell lines were negative (MDA-MB-231, MDA-MB-435, MDA-MB-468, and MCF7). When stably reintroduced into CLCA2-negative MDA-MB-231 and MDA-MB-435 cells, CLCA2 expression reduced Matrigel invasion in vitro and inducibility of s.c. and metastatic tumors of MDA-MB-231 cells in nude mice. Our results suggest that CLCA2 may act as a tumor suppressor in breast cancer.
Gruber
A D
AD
Department of Molecular Medicine, Cornell University College of Veterinary Medicine, Ithaca, New York 14853-6401, USA.
Pauli
B U
BU
D000818:Animals; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D000090007:CLC-2 Chloride Channels; D002118:Calcium / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000090007:CLC-2 Chloride Channels; C120066:CLCA2 protein, human; D018118:Chloride Channels; C492299:Clca2 protein, mouse; C000715428:Clcn2 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D002118:Calcium