| Autor: |
Hollestelle, Antoinette, Elstrodt, Fons, Timmermans, Mieke, Sieuwerts, Anieta, Klijn, Jan, Foekens, John, Bakker, Michael, Schutte, Mieke |
| Zdroj: |
Breast Cancer Research & Treatment; Jul2010, Vol. 122 Issue 1, p125-133, 9p |
| Abstrakt: |
Mutations of E-cadherin 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 E-cadherin gene mutations in the lobular breast cancer phenotype was recently demonstrated in E-cadherin 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 E-cadherin genes. Here, we identified E-cadherin 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 α-catenin mutations among 55 human breast cancer cell lines. All four α-catenin 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 α-catenin mutant cell lines had the rounded cell morphology and all 14 cell lines with the rounded cell morphology had mutations of either E-cadherin or α-catenin. As anticipated, loss of α-catenin protein expression was associated with the lobular subtype in primary breast cancers. Together, our observations suggest that α-catenin may be a new tumor suppressor gene that operates in the E-cadherin tumor suppressor pathway. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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