Scientists tie several cancers to common 'oncogene engine' ( trial. The transcription factor fa...)

Scientists tie several cancers to common 'oncogene engine'

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The transcription factor family is collectively known as MiT. Its kingpin, a protein called MITF, is needed by the body to develop normally functioning melanocytes, the pigment-producing cells of the skin and hair. Mutations that disable MITF cause lack of pigment, as in albinism, but when the gene for MITF is amplified ?too many copies in a cell ?it can cause melanoma, because the growth genes that are regulated by MITF act like a stuck "on" switch for cell proliferation. Last year, investigators based at Dana-Farber (including Fisher and his colleagues) reported that the MITF gene is amplified in 20 percent of melanoma tumors.

In addition, Fisher and Scott R. Granter, MD, of Children's Hospital Boston ?also an author of the Cancer Cell article ?previously found that MITF was present in a dangerous type of soft-tissue tumor ?clear cell sarcoma ?that develops near muscles and tendons in teenagers and young adults. The scientists had been alerted to the possibility of MITF involvement because clear cell sarcoma tumors are sometimes pigmented ?a process requiring the MITF transcription factor. In this form of sarcoma, Fisher explained, the MITF gene is overactivated by an abnormal joining, or fusion, of two other genes. MITF, in turn, is directly responsible for malignant growth and survival of the cells. Suppression of MITF by genetic means in the laboratory is lethal to clear cell sarcoma.

While no drug currently exists to directly suppress MITF, the identification of MITF's role opens a door to potential therapies because the researchers have identified some of the genes and proteins that MITF regulates that new drugs could be used to block. One of the targets is Bcl-2, which enables cancer cells to survive when the body has ordered them to self-destruct, and another is CDK-2, a protein that is often abnormal in cancer.

Related to MITF in the MiT transcription factor family are three proteins named TFEB, TFE3, and TFEC. One
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Source:Dana-Farber Cancer Institute

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