PAX6 suppresses growth of human glioblastoma cells (original) (raw)

Abstract

Purpose: Glioblastomas (GBMs) are the most common primary malignant brain tumors. Majority of GBMs has loss of heterozygosity of chromosome 10. The PAX6 encodes a transcription factor that involves in development of the brain, where its expression persists. We have reported that the expression of PAX6 was significantly reduced in GBMs and that a low level of PAX6 expression is a harbinger of an unfavorable prognosis for patients with malignant astrocytic glioma. Interestingly, PAX6 expression was increased in suppressed somatic cell hybrids derived from introducing a normal human chromosome 10 into U251 GBM cells. Thus it is interesting to determine if repression of PAX6 expression is involved in anti-tumor suppression function in GBM.

Experimental design: We overexpressed PAX6 in a GBM cell line U251HF via either stable transfection or infection with recombinant adenovirus, and examined cell growth in vitro and in vivo.

Result: Although we did not observe changes in the cell doubling time for _PAX6-_stable transfectants, significantly fewer numbers of _PAX6_-positive colonies grew in soft agar. Transient overexpression of PAX6 via adenovirus, however, suppressed cell growth by increasing the number of cells in G1 and by decreasing the number of cells in S-phase, and later on caused a dramatic level of cell death. Repeated subcutaneous and intracranial implantation experiments in nude mice using _PAX6_-stable transfectants provided solid evidence that PAX6 suppressed tumor growth in vivo and significantly extended mouse survival.

Conclusion: Our data demonstrate that _PAX6_exerts a tumor suppressor function that limits the growth of GBM cells.

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Abbreviations

AA:

anaplastic astrocytoma

GBM:

glioblastoma multiforme

P.I:

propidium iodide

QRT-PCR:

quantitative reverse transcriptase-polymerase chain reaction

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Authors and Affiliations

1. Department of Neurobiology and Developmental Sciences, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, 4301 West Markham, Slot 753, Little Rock, AR, 72205, USA
   Yi-Hong Zhou & Xiaosong Wu
2. Department of Neuro-Oncology, Anderson Cancer Center, University of Texas M.D., Houston, TX, USA
   Fang Tan, Yue-Xi Shi, Tricia Glass, T. J. Liu & W. K. Alfred Yung
3. Department of Biostatistics, Anderson Cancer Center, University of Texas M.D., Houston, TX, USA
   Kyle Wathen & Kenneth R. Hess
4. Department of Neurosurgery, Anderson Cancer Center, University of Texas M.D., Houston, TX, USA
   Joy Gumin & Frederick Lang

Authors

1. Yi-Hong Zhou
2. Xiaosong Wu
3. Fang Tan
4. Yue-Xi Shi
5. Tricia Glass
6. T. J. Liu
7. Kyle Wathen
8. Kenneth R. Hess
9. Joy Gumin
10. Frederick Lang
11. W. K. Alfred Yung

Corresponding author

Correspondence toYi-Hong Zhou.

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Zhou, YH., Wu, X., Tan, F. et al. PAX6 suppresses growth of human glioblastoma cells.J Neurooncol 71, 223–229 (2005). https://doi.org/10.1007/s11060-004-1720-4

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• Accepted: 17 June 2004
• Issue date: February 2005
• DOI: https://doi.org/10.1007/s11060-004-1720-4

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