Casein kinase I epsilon somatic mutations found in breast cancer cause overgrowth in Drosophila

0434963 - BC 2015 RIV ES eng J - Článek v odborném periodiku
Doležal, Tomáš - Kučerová, K. - Neuhold, J. - Bryant, P. J.
Casein kinase I epsilon somatic mutations found in breast cancer cause overgrowth in Drosophila.
International Journal of Developmental Biology. Roč. 54, č. 10 (2010), s. 1419-1424. ISSN 0214-6282. E-ISSN 1696-3547
Grant CEP: GA ČR GA301/07/0814
Výzkumný záměr: CEZ:AV0Z50070508
Klíčová slova: Drosophila * breast cancer * Dco
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 2.856, rok: 2010
http://www.ijdb.ehu.es/web/paper.php?doi=093032td

We are using a candidate gene approach to identify genes contributing to cancer through somatic mutation. Somatic mutations were found in breast cancer samples in the human casein kinase I epsilon (CKI epsilon) gene, a homolog of the Drosophila gene dco in which certain point mutations lead to imaginal disc overgrowth. We therefore created fly genotypes in which the dco gene carried point mutations homologous to those discovered in CKI epsilon, and tested them in vivo. The results show that the most frequent mutation discovered in breast cancer, L39Q, causes a striking overgrowth phenotype in flies. Further experiments show that this mutation affects the newly recognized Fat/Warts signaling pathway, which controls organ size and shape in both flies and mammals. Another mutation, S101R, modifies the mutant phenotype so that the affected tissue disintegrates, mimicking more aggressive forms of breast cancer. Our results thus strongly support the conclusion that CKI epsilon mutations play important roles in breast carcinogenesis.
Trvalý link: http://hdl.handle.net/11104/0238947