Gene's 'Jekyll and Hyde' role in brain cancer discovered

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Washington, February 7 : While many scientists believe that disrupted activity of a gene called STAT3 leads to the brain cancer glioblastoma, Harvard Medical School researchers have found that the same gene plays the role of a tumour suppressor in certain cases.

Writing about their findings in the journal Genes and Development, the researchers said that the same gene in the same cancer could play a completely different role from one person to the next, depending on genetic nuances between individuals.

"This discovery lays the foundation for a more tailored therapeutic intervention. And that's really important. You can't just go blindly treating people by inhibiting STAT3," says study's senior author Azad Bonni, an associate professor of pathology at Harvard Medical School, and senior author on this study.

Well informed that most brain cancers occur in a class of brain cells called astrocytes, the researchers decided to investigate the genetic etiology of glioblastoma by studying whether certain regulatory genes that control the generation of astrocytes during normal development also play a role in these tumours.

The researchers focussed their attention to STAT3 because it is a key gene that turns neural stem cells in to astrocytes during normal development.

They first genetically manipulated mouse astrocytes, and later placing them into a second group of mice whose immune systems had been compromised.

With the help of previously published data, the researchers examined how two genes called EGFR and PTEN, whose mutated forms are associated with glioblastoma, affect the function of STAT3 in astrocytes.

It was found that STAT3 triggers cancer development when EGFR is mutated, whereas it acts as a tumour suppressor with a PTEN mutation.

The researchers confirmed the same findings in human glioblastoma tumors as well.

"The belief that STAT3 can only be an oncogene (which causes cancer) has been a pretty entrenched dogma in the field, so we performed many, many experiments to make sure this was correct. It took some very persistent investigators in my lab to get the job done. As a result, we're convinced of our data," says Bonni.

The researchers say that their findings may also have applicability to prostate and breast cancers, as STAT3 has also been implicated in these forms of cancer.

In addition, the findings contribute to the growing body of evidence for "personalized medicine," showing that many types of cancers contain subgroups that require different treatments.

ANI

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