Role of Wnt5a in the proliferation of human glioblastoma cells.
Wnt5a operates as either a tumor suppressor or a tumor stimulator, according to tumor type. The functions of Wnt5a in human glioblastoma (GBM) have yet to be determined. We initially evaluated the expression of Wnt5a in human glioma. The results of immunohistochemical analyses have revealed that Wnt5a expression was higher in human GBM than in normal brain tissue and low-grade astrocytoma. In order to assess the role of Wnt5a on proliferation in human glioblastoma cells, we employed U87MG and GBM-05, a newly established GBM cell line. GBM-05 was established from a patient diagnosed with GBM. GBM-05 cells were shown to express Nestin, but did not express GFAP and Map2ab. GBM-05 cells formed infiltrating brain tumors after being intracerebrally transplanted into nude mice, and xenotransplanted GBM-05 cells were observed to differentiate into neuronal and astrocyte lineages. Wnt5a expression in the xenotransplanted tumors was higher than that detected in the surrounding brain tissues. The overexpression of Wnt5a increased the proliferation of GBM-05 and U87MG in vitro. By way of contrast, the downregulation of Wnt5a expression as the result of RNA interference reduced proliferation from GBM-05 and U87MG cells in vitro, and reduced tumorigenicity in vivo. Our data indicate that Wnt5a signaling is an important regulator in the proliferation of human glioma cells.
Yu
Ji Min
JM
Department of Physiology, School of Medicine, Pusan National University, Pusan 602-739, Republic of Korea.
Jun
Eun Sook
ES
Jung
Jin Suk
JS
Suh
Su Young
SY
Han
Jin Young
JY
Kim
Jee Yeon
JY
Kim
Ki Wook
KW
Jung
Jin Sup
JS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis; D007621:Karyotyping; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014183:Transplantation, Heterologous; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071818:Wnt-5a Protein
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein