NEW YORK (Reuters Health) - Reduced expression of tumor suppressor promyelocytic leukemia (PML) protein is associated with tumor progression in a number of human cancers, not exclusively in acute promyelocytic leukemia, researchers report in the February 18th issue of the Journal of the National Cancer Institute.
As senior investigator Dr. Pier Paolo Pandolfi told Reuters Health, “PML was so far thought to oppose the formation of a specific form of leukemia. Now we know that PML can antagonize tumor formation in many organs.”
Dr. Pandolfi of Memorial Sloan-Kettering Cancer Center, New York and colleagues came to this conclusion after using tissue microarrays to examine samples from a wide variety of solid tumors.
All normal tissues expressed PML protein, but expression was reduced or abolished in prostate adenocarcinomas, colon adenocarcinomas, lung carcinomas and CNS and other tumors. However, this was not the case in thyroid or adrenal carcinomas.
Loss of PML expression was associated with tumor progression in prostate cancer. Complete loss was associated with progression from prostatic intraepithelial neoplasia to invasive carcinoma.
In breast cancer, complete loss was associated with lymph node metastasis, and in CNS tumors, complete loss was associated with high-grade tumors.
Nevertheless, say the researchers, PML mRNA was expressed in all tumor and cell line samples and the PML gene was “rarely mutated” and was not subject to loss of heterozygosity.
In light of these results, continued Dr. Pandolfi, the loss of PML function is an important event in the genesis of prevalent human cancers.
“These findings,” he added, also have “potential therapeutic implications as we have means to pharmacologically restore normal PML protein levels.”
Source: J Natl Cancer Inst 2004;96:269-279. [ Google search on this article ]
MeSH Headings:Biological Sciences: Biology: Gene Expression Regulation: Genetics: Genetics, Biochemical: Molecular Biology: Biological SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
