TY - JOUR
T1 - NFIA and NFIB function as tumour suppressors in high-grade glioma in mice
AU - Chen, Kok Siong
AU - Lynton, Zorana
AU - Lim, Jonathan W.C.
AU - Robertson, Thomas
AU - Gronostajski, Richard M.
AU - Bunt, Jens
AU - Richards, Linda J.
N1 - Funding Information:
The research was funded by the National Health and Medical Research Council (Grant numbers GNT1100443, GNT1120615 to L.J.R.); Tour de Cure (Scott Canner Young Research Grant to J.B.); the Brain Foundation (Research gift to J.B.); Ride for Rhonda (Research gift to L.J.R. and J.B.); and NYSTEM (Contract C030133 to R.M.G.). Students were supported by the University of Queensland (International Postgraduate Student Scholarship to K.S.C., UQ Queensland Graduate School Scholarship to Z.L., UQ Centennial Scholarship to J.W.C.L.); Australian Government (Research Training Program Scholarship to J.W.C.L.); and the Royal College of Pathologists of Australasia (Medical Student Scholarship to Z.L.).
Publisher Copyright:
© 2020 The Author(s).
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Nuclear factor one (NFI) transcription factors are implicated in both brain development and cancer in mice and humans and play an essential role in glial differentiation. NFI expression is reduced in human astrocytoma samples, particularly those of higher grade, whereas over-expression of NFI protein can induce the differentiation of glioblastoma cells within human tumour xenografts and in glioblastoma cell lines in vitro. These data indicate that NFI proteins may act as tumour suppressors in glioma. To test this hypothesis, we generated complex mouse genetic crosses involving six alleles to target gene deletion of known tumour suppressor genes that induce endogenous high-grade glioma in mice, and overlaid this with loss of function Nfi mutant alleles, Nfia and Nfib, a reporter transgene and an inducible Cre allele. Deletion of Nfi resulted in reduced survival time of the mice, increased tumour load and a more aggressive tumour phenotype than observed in glioma mice with normal expression of NFI. Together, these data indicate that NFI genes represent a credible target for both diagnostic analyses and therapeutic strategies to combat high-grade glioma.
AB - Nuclear factor one (NFI) transcription factors are implicated in both brain development and cancer in mice and humans and play an essential role in glial differentiation. NFI expression is reduced in human astrocytoma samples, particularly those of higher grade, whereas over-expression of NFI protein can induce the differentiation of glioblastoma cells within human tumour xenografts and in glioblastoma cell lines in vitro. These data indicate that NFI proteins may act as tumour suppressors in glioma. To test this hypothesis, we generated complex mouse genetic crosses involving six alleles to target gene deletion of known tumour suppressor genes that induce endogenous high-grade glioma in mice, and overlaid this with loss of function Nfi mutant alleles, Nfia and Nfib, a reporter transgene and an inducible Cre allele. Deletion of Nfi resulted in reduced survival time of the mice, increased tumour load and a more aggressive tumour phenotype than observed in glioma mice with normal expression of NFI. Together, these data indicate that NFI genes represent a credible target for both diagnostic analyses and therapeutic strategies to combat high-grade glioma.
UR - http://www.scopus.com/inward/record.url?scp=85105688264&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgaa139
DO - 10.1093/carcin/bgaa139
M3 - Article
C2 - 33346791
AN - SCOPUS:85105688264
SN - 0143-3334
VL - 42
SP - 357
EP - 368
JO - Carcinogenesis
JF - Carcinogenesis
IS - 3
ER -