CLDF Title
Home | Contact Us | Bookmark
About CLDF Centers of Educational Expertise  
Live CME Meetings Webcasts Slide Library Abstract Library Conference Highlights
Reuters Health Information (2007-01-24): Reactivation of p53 tumor suppressor gene causes tumor regression


Reactivation of p53 tumor suppressor gene causes tumor regression

Last Updated: 2007-01-24 14:40:47 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Inactivation of the p53 tumor suppressor gene, usually by mutation, is one way tumor formation is initiated. Now, two studies present data supporting a curative effect of restoring normal p53 function.

According to the reports in Nature, published online on January 25, restoration of normal endogenous p53 activity, even for a short time, causes tumor regression. Depending on the tumor type, reactivated p53 can cause apoptosis, decreased proliferation, or cellular senescence.

Dr. Scott W. Lowe, from Cold Spring Harbor Laboratory in New York, and his associates note that p53 normally restricts proliferation in response to DNA damage or deregulation of mitogenic oncogenes. When p53 is mutated, cell proliferation and longevity is increased. At times, the lack of p53 activity also promotes genomic instability and resistance to some chemotherapeutic agents.

To investigate the potential of p53 restoration, Dr. Lowe's group generated hepatoblasts bearing inactive p53, which could be restored by exposure to doxycycline. When they implanted oncogenic hepatoblasts lacking p53 activity into the livers of mice, invasive hepatocarcinomas developed.

Once tumors reached an advanced stage, addition of doxycycline reestablished p53 expression, tumors rapidly involuted and were nearly undetectable within 12 days. As little as 4 days of treatment with doxycycline was sufficient to induce irreversible tumor involution in subcutaneous tumors, Dr. Lowe's group reports, suggesting that the process of involution "seems irreversible."

"Surprisingly," they found that p53 activation did not appear to induce apoptosis in the liver tumors, but instead caused decreased proliferation associated with signs of cellular differentiation.

Dr. Tyler Jacks, at Massachusetts Institute of Technology in Cambridge, and his team investigated the same issues using null mice carrying a p53 knockout allele that could be reactivated.

After restoring endogenous p53 expression in the mice, autochthonous lymphomas underwent apoptosis. Sarcomas, on the other hand, responded to p53 reactivation by cell cycle arrest and cellular senescence.

Dr. Jacks' team suggests that pharmacological strategies to restore p53 function may eliminate human tumors maintained by p53 inactivation.

Other strategies to reactivate p53 include the use of small molecules to restore point mutations in p53 and thus produce a transcriptionally competent p53 protein, or gene therapy to induce a wild-type copy of the p53 gene into tumor cells.

Nature 2007;445.

Slide Library
Abstract Library
Slide Library
Abstract Library
Slide Library
Abstract Library
Slide Library
Abstract Library
Slide Library
Abstract Library
Slide Library
Abstract Library
Slide Library
About CLDF
Mission Statement
Board of Trustees
Board of Advisors
CLDF Sponsors & Supporters
Other Resources
Liver News Library
Journal Abstracts
Hep C Link to Care
Centers of
Educational Expertise
Substance Use Disorder
CLDF Follow Us
  The Chronic Liver Disease Foundation is a non-profit organization with content developed specifically for healthcare professionals.
© Copyright 2012-2018 Chronic Liver Disease Foundation. All rights reserved. This site is maintained as an educational resource for US healthcare providers only.
Use of this Web site is governed by the Chronic Liver Disease Foundation terms of use and privacy statement.