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Advances in Brief

Loss of Wild-Type p53 Bestows a Growth Advantage on Primary Cortical Astrocytes and Facilitates Their in Vitro Transformation

Oliver Bögler, H-J. Su Huang and Webster K. Cavenee
Oliver Bögler
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H-J. Su Huang
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Webster K. Cavenee
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DOI:  Published July 1995
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Abstract

Primary cortical astrocytes were isolated from normal (+/+), heterozygous (+/-), or homozygous (-/-) p53-knockout mice. The normal astrocytes grew slowly and underwent crisis after limited division, while the homozygously defective cells grew rapidly and without contact inhibition. These -/- cells could not initially form colonies in soft agarose but acquired this capability after 10 passages in FCS or basic fibroblast growth factor but not epidermal growth factor. Almost all -/- astrocytes weakly expressed glial fibrillary acidic protein at passage 10 and were also A2B5+ when cultured in basic fibroblast growth factor. Most heterozygous cells resembled normal ones; however, some survived crisis, grew rapidly, and formed colonies. Outgrowing cells had all lost the wild-type p53 allele. These molecular and cellular events mimic the early stages of human brain tumors, suggest a role for p53 in the earliest stages of disease progression, and provide an experimental system to analyze the effects of other tumor-specific mutations in the disease process.

Footnotes

  • ↵1 Supported by the California Division of the American Cancer Society, Fellowship 1-62-95 (to O. B.).

  • ↵2 To whom requests for reprints should be addressed, at Ludwig Institute for Cancer Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660.

  • Received May 3, 1995.
  • Accepted May 19, 1995.
  • ©1995 American Association for Cancer Research.
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July 1995
Volume 55, Issue 13
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Loss of Wild-Type p53 Bestows a Growth Advantage on Primary Cortical Astrocytes and Facilitates Their in Vitro Transformation
Oliver Bögler, H-J. Su Huang and Webster K. Cavenee
Cancer Res July 1 1995 (55) (13) 2746-2751;

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Loss of Wild-Type p53 Bestows a Growth Advantage on Primary Cortical Astrocytes and Facilitates Their in Vitro Transformation
Oliver Bögler, H-J. Su Huang and Webster K. Cavenee
Cancer Res July 1 1995 (55) (13) 2746-2751;
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