Glioblastoma formation from cell population depleted of Prominin1-expressing cells.
Prominin1 (Prom1, also known as CD133 in human) has been widely used as a marker for cancer stem cells (CSCs), which self-renew and are tumorigenic, in malignant tumors including glioblastoma multiforme (GBM). However, there is other evidence showing that Prom1-negative cancer cells also form tumors in vivo. Thus it remains controversial whether Prom1 is a bona fide marker for CSCs. To verify if Prom1-expressing cells are essential for tumorigenesis, we established a mouse line, whose Prom1-expressing cells can be eliminated conditionally by a Cre-inducible DTA gene on the Prom1 locus together with a tamoxifen-inducible CreER(TM), and generated glioma-initiating cells (GICs-LD) by overexpressing both the SV40 Large T antigen and an oncogenic H-Ras(L61) in neural stem cells of the mouse line. We show here that the tamoxifen-treated GICs-LD (GICs-DTA) form tumor-spheres in culture and transplantable GBM in vivo. Thus, our studies demonstrate that Prom1-expressing cells are dispensable for gliomagenesis in this mouse model.
Nishide
Kenji
K
Department of Biology, Graduate School of Science, Kobe University, Kobe, 657-8601, Japan. [corrected]
Nakatani
Yuka
Y
Kiyonari
Hiroshi
H
Kondo
Toru
T
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers; D055879:Gene Knock-In Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000235:genetics*; D019426:Integrases / Q000235:genetics; D051379:Mice; D010455:Peptides / Q000235:genetics*
D000071916:AC133 Antigen; D015703:Antigens, CD; D017931:DNA Primers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C045073:Cre recombinase; D019426:Integrases