Metabolic 'reprogramming' by the p53 gene family leads to tumor regression
Posted: November 17, 2014 at 3:44 pm
PUBLIC RELEASE DATE:
17-Nov-2014
Contact: Ron Gilmore rlgilmore1@mdanderson.org 713-745-1898 University of Texas M. D. Anderson Cancer Center @mdandersonnews
Scientists have found that altering members of the p53 gene family, known as tumor suppressor genes, causes rapid regression of tumors that are deficient in or totally missing p53. Study results suggest existing diabetes drugs, which impact the same gene-protein pathway, might be effective for cancer treatment.
The University of Texas MD Anderson Cancer Center investigation showed that, in vivo, the genes p63 and p73 can be manipulated to upregulate or increase levels of IAPP, a protein important for the body's ability to metabolize glucose. IAPP is found in some diabetes drugs already on the market.
The research findings were published in today's issue of Nature.
The study, led by Elsa R. Flores, Ph.D., associate professor of molecular and cellular oncology, centered on p63 and p73 because of the genes' ability to cause tumor regression or spur its growth due to their unique genetic makeup.
"P53 is altered in most human cancers and p53 reactivation suppresses tumors in vivo in mice. This strategy has proven difficult to implement therapeutically. We examined an alternative approach by manipulating the p53 family members, p63 and p73," said Flores.
Flores described two "warring" versions of p63 and p73 that are at odds when it comes to tumor suppression. One version, known as transactivation domain-bearing, is structurally and functionally similar to p53 in their ability to suppress tumors. The other version, which lacks this transactivation domain, actually prevents p53 from stopping tumor growth. Transactivation domains are specific regions within a protein known as a transcription factor that effect further downstream cellular responses.
"The p53 family interacts extensively in cellular processes that promote tumor suppression," said Flores. "Thus, a clear understanding of this interplay in cancer is needed to treat tumors with p53 alterations."
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Metabolic 'reprogramming' by the p53 gene family leads to tumor regression