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Building a better mouse model of lung cancer: FHIT counts

Scientists have identified some of the very earliest genetic changes involved in the development of lung cancer and have incorporated them into a new strain of mouse that develops the disease in much the same way that humans do.

The discoveries, reported in the August 1 issue of Cancer Research, open the door to the possibility of new, targeted treatments that could be offered at the very first signs of lung cancer, when the possibility of a cure is most likely.

Creating the new mouse was basically a matter of FHIT ?the gene that forms the cornerstone of the new model ?according to Kay Huebner, a professor of molecular virology, immunology and medical genetics and a researcher in Ohio State University 's Comprehensive Cancer Center (OSUCCC). Huebner, the senior author of the study, has studied FHIT for years, noting it is one of several tumor suppressor genes residing on chromosome 3 in humans that, when working normally, keep any potentially cancerous cells from growing out of control.

But when mutations or alterations eliminate one or both copies of the FHIT gene, the "brakes" that control cell growth are released, allowing potentially cancerous lesions to become malignant.

Studies show that very early in the development of lung cancer, the FHIT gene loses its ability to produce a specific protein (called Fhit). This same loss has been linked to head and neck, esophageal, colorectal, breast and cervical cancers as well.

Because the loss of FHIT occurs so early in lung cancer, mice that are missing that gene may be a good model in which to test new ways to treat or prevent the disease, says Huebner. "There are some other useful mouse models out there, but they generally reflect genetic mutations that happen later in the disease, when tumors are clearly visible and successful treatment unlikely," says Huebner. "We were interested in creating a model that reflected the timing and order of genetic and epigenetic changes in the hu
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Source:Ohio State University


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