Researchers have identified a new growth factor from mousepancreatic beta cell tumors that is a potent mitogen, and couldplay a role in pancreatic cancers and contribute to the vascularcomplications associated with diabetes.
Scientists from Harvard Medical School in Boston, theUniversity of California, San Francisco (UCSF) and Japan'sTakeda Chemical Industries report in today's issue of Sciencethat this new factor, betacellulin, is a member of the epidermalgrowth factor family and can induce mitosis in retinal pigmentepithelial cells and vascular smooth muscle cells.
In an effort to understand the molecular mechanisms that leadto tumorigenesis -- including angiogenesis -- the researchers"sought to identify molecules secreted by tumor cells that havemitogenic activity on one or another of the cell types involvedin tumor growth." In the process they came up withbetacellulin.
Gerhard Christofori, one of the authors of the report and apostdoctoral fellow in co-author Douglas Hanahan's lab atUCSF's Hormone Research Institute, told BioWorld, "We haveother mitogens secreted by these tumor cell lines (which weredeveloped from murine pancreatic beta cell carcinomas, orinsulinomas), but they are known already" -- acidic fibroblastgrowth factor, angiogenic factors and others, for example.Betacellulin, however, "hasn't been characterized before."
The researchers cloned the cDNA for mouse betacellulin anddetermined its nucleotide sequence. They determined thatbetacellulin is derived from a larger precursor protein,probably embedded in the cellular membrane.
They also found the messenger RNA for this factor in normalmouse tissue, other mouse tumor cell lines and even humantumor cell lines. "It's widely expressed in normal mouse tissue,as well, but we don't yet know by which cell type," Christoforiexplained.
The researchers found betacellulin in mouse thymus, lung,heart, liver, spleen, small intestine, pancreas, kidney, muscle,testis and uterus. They also found it in mouse sarcoma andfibrosarcoma cell lines, and isolated a human homolog ofbetacellulin cDNA from a breast adenocarcinoma cell line.
The researchers concluded: "Our finding that this growth factoris expressed in insulinomas and certain other tumor cell linessuggests that it may contribute to the phenotype of thesecancers. The structural characteristics of betacellulin indicatethat it is produced from a precursor molecule by proteolyticcleavage, which raises the possibility of tissue-specificregulation through protease activation."
-- Jennifer Van Brunt Senior Editor
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