AsianScientist (May 16, 2011) – An international team of researchers from the University of California – San Diego and the Eastern Hepatobiliary Surgery Hospital in China say a human gene implicated in the development of leukemia also acts to prevent cancer of the liver.
Published this week in Cancer Cell, Dr. Gen-Sheng Feng and colleagues report that an enzyme produced by the human gene PTPN11 appears to help protect hepatocytes (liver cells) from toxic damage and death. Conversely, the same enzyme, called Shp2, is a known factor in the development of several types of leukemia.
“The new function for PTPN11/Shp2 as a tumor suppressor in hepatocellular carcinoma (HCC) stands in contrast to its known oncogenic effect in leukemogenesis,” said Feng. “It’s a surprising finding, but one that we think provides a fresh view of oncogenesis. The same gene can have oncogenic or anti-oncogenic effects, depending upon cellular context.”
Previous studies had determined that PTPN11 was a proto-oncogene. That is, dominant active mutations in the gene had been identified in several types of leukemia patients, as was an over-expression of the gene product Shp2. Feng and colleagues looked to see what happened when Shp2 was knocked out specifically in hepatocytes in a mouse model.
The result wasn’t good: The mice got liver cancer.
Strikingly, deficient or low expression of PTPN11 was detected in a sub-fraction of human HCC patient samples by researchers at the Eastern Hepatobiliary Surgery Hospital in Shanghai, China.
“Removing Shp2 from these liver cells leads to their death, which in turn triggers compensatory regeneration and inflammatory responses. That results in enhanced development of HCC induced by a chemical carcinogen,” said Dr. Hongyang Wang who led the Chinese team.
Feng said the findings highlight the unique mechanism underlying HCC, but more broadly, they reveal new complexities in how different types of cancer begin. Indeed, the researchers say their work also uncovered pro- and anti-oncogenic activities in a gene transcription factor called Stat3 – Stat3 promotes HCC development, but deleting it also resulted in a modest, but significant, increase in HCC.
In conclusion, the results in this paper underscore the need for caution in designing therapeutic strategies for treating HCCs and other types of cancers because the answer might also be the problem.
The article can be found at: Bard-Chapeau EA et al. (2011) Ptpn11/Shp2 Acts as a Tumor Suppressor in Hepatocellular Carcinogenesis.
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Source: UCSD.
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