Protein-A Breast Cancer Tumor Suppressor.


Logos 005A new study published recently in online Oncogene concluded that  HOXA5 protein in normal breast cells acts as a tumor suppressor that halts abnormal cell growth. This builds upon  previous research finding that many breast cancer patients have a lower level of HOXA5 protein, a gene product known to control cell differentiation and death, and lower levels of the protein corresponded to poorer outcomes for patients.

In the study, researchers analyzed gene expression from human breast cell lines lacking HOXA5 and found that the protein seems to help maintain several traits in normal breast cancer, including the ability to adhere to other epithelial cells, and the presence of molecules marking the cells as differentiated and not capable of self-renewal like breast stem cells. When they depleted the HOXA5 proein in other breast cell lines in the lab, the cells became more immature, or stemlike, as well as more mobile. They also found that HOCA3 regulates the production of two other proteins, CD24 and E-cadherin, cells, without CD24, the cells begin to revert toward a stem like state, and without E-cadherin, cells lose some of the glue that binds them to other cells.  Consequently, breast cells without HOXA5 were more likely to grow aggressively in lab experiments forming structures similar to those seen as tumor cells ready to metastasize.

After injecting human tumor cells with and without HOXA5 into the mammary fat pad of mice they found that tumor cells containing protein carried anywhere from 10 to 17 times fewer breast stem cells, and tumor growth from the injected cells were about 3 times smaller than those in mice who received tumor cells with depleted levels of HOXA5. Further research is planned on breast cancer and the role of HOXA5,

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