Expression and function of vinculin in neuroendocrine tumors.
Transfection of chicken vinculin into highly malignant neuroendocrine tumor cells, vasostatin-transformed (vaso-transformed) Bon cells which expressed low levels of vinculin protein, reversed their malignant behavior and restored expression of tumor suppressor genes. Conversely, small interfering RNA (siRNA)-mediated knockout of vinculin resulted in fast cell growth and augmentation of colony formation in wild-type cells. Moreover, expression of a tight junction protein, claudin 4 (CLD4), was found to be associated with vinculin expression. In the vaso-transformed Bon cells, CLD4 expression was reduced, whereas a significantly increased CLD4 expression was observed in the cells with vinculin overexpression. Furthermore, vinculin knockout brought about CLD4 downregulation in wild-type cells. However, vinculin and CLD4 expression was inversely correlated in neuroendocrine tumors, respectively. Based on these findings, we hypothesize that vinculin plays a role in growth regulation of neuroendocrine tumors. Further studies are necessary to analyze the relationship between the course of the disease, and vinculin and CLD4 expression in large tumor samples.
Liu
Minghui
M
Endocrine Oncology Unit, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Oberg
Kjell
K
Zhou
Yinghua
Y
D037282:Calreticulin / Q000378:metabolism; D002448:Cell Adhesion; D049109:Cell Proliferation; D062506:Claudin-4; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D016596:Vinculin / Q000096:biosynthesis* / Q000378:metabolism
C568157:CLDN4 protein, human; D037282:Calreticulin; D062506:Claudin-4; D008565:Membrane Proteins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C121986:vasostatin; D016596:Vinculin; D049452:Green Fluorescent Proteins