Four human breast cancer cell lines with biallelic inactivating gene mutations
Résumé
Mutations of have been identified in half of lobular breast cancers and diffuse-type gastric cancers, two tumor subtypes with remarkably similar pathological appearances including small rounded cells with scant cytoplasm and a diffuse growth pattern. A causal role for gene mutations in the lobular breast cancer phenotype was recently demonstrated in knock-out mice. These observations suggested that another gene in the E-cadherin tumor suppressor pathway might be mutated in lobular breast cancers with wild-type genes. Here, we identified gene mutations exclusively in human breast cancer cell lines that grow with a rounded cell morphology. Using expression analyses and gene mutation analyses, we have identified four biallelic inactivating mutations among 55 human breast cancer cell lines. All four mutations predicted premature termination of the encoded proteins, and concordantly, none of the four mutant cell lines expressed α-catenin proteins. Importantly, three of the mutant cell lines had the rounded cell morphology and all 14 cell lines with the rounded cell morphology had mutations of either or . As anticipated, loss of α-catenin protein expression was associated with the lobular subtype in primary breast cancers. Together, our observations suggest that may be a new tumor suppressor gene that operates in the E-cadherin tumor suppressor pathway.
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