DEAR1 gene may help drive early-onset breast cancer
(25 May 2009: VIDYYA MEDICAL NEWS SERVICE) -- In a new study led by researchers at the University of Texas M.D. Anderson Cancer Center, a gene has been identified that regulates the development of the cells that form milk-secreting glands in the breast. The gene, called DEAR1, is mutated or not expressed in many cases of early-onset breast cancer, and it may also serve as a biomarker for identifying patients at high risk of local recurrence.
After using a technique called suppression subtractive hybridization to identify DEAR1 as a gene of interest, the researchers tested cell lines and tissue samples to determine its role in breast cancer. Expression of DEAR1 was absent or reduced in six out of eight breast cancer cell lines examined; in addition, 13 percent of 55 primary breast tumor samples tested contained DEAR1 mutations.
The researchers used gene-transfer techniques to restore DEAR1 expression in a breast cancer cell line. Without DEAR1, over 60 percent of the cultured cells formed large, disorganized structures. With the introduction of DEAR1, more than 80 percent of cells produced small, normal-shaped structures. When the gene was silenced in normal breast cells, they failed to form normal structures and instead showed morphology similar to breast cancer cells.
The researchers screened tissue samples from 158 premenopausal women with breast cancer and found that 56 percent of the tumor samples had completely lost DEAR1 expression, noting that this “correlated with a strong family history of breast cancer in this young cohort.” Loss of DEAR1 expression also correlated significantly with triple-negative breast cancer, which is the most difficult type to treat successfully.
Because DEAR1 expression was also a significant prognostic marker for local recurrence in early-onset tumors, the authors suggested that measurement of DEAR1 expression “could be an important marker to stratify early-onset breast cancer patients for increased vigilance in follow-up and adjuvant therapy.”
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