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Cancer Res ; 61(21): 7978-84, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11691822

RESUMO

A second adenomatous polyposis coli (APC)-like gene, APC2/APCL, was recently described and localized to chromosome 19. We have fine mapped APC2 to a small region of chromosome 19p13.3 containing markers D19S883 and WI-19632, a region commonly lost in a variety of cancers, particularly ovarian cancer. Interphase fluorescence in situ hybridization analysis revealed an APC2 allelic imbalance in 19 of 20 ovarian cancers screened and indicates that APC2 could be a potential tumor suppressor gene in ovarian cancer. When overexpressed in SKOV3 ovarian cancer cells, which express low levels of APC2, exogenous APC2 localized to the Golgi apparatus, actin-containing structures, and occasionally to microtubules. Antibodies against the NH2 terminus of human APC2 show that endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. APC2 remained associated with actin filaments after treatment with the actin-disrupting agent, cytochalasin D. These results suggest that APC2 is involved in actin-associated events and could influence cell motility or adhesion through interaction with actin filaments, as well as functioning independently or in cooperation with APC to down-regulate beta-catenin signaling.


Assuntos
Desequilíbrio Alélico , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Cromossomos Humanos Par 19/genética , Proteínas do Citoesqueleto/biossíntese , Cães , Feminino , Expressão Gênica , Genes APC , Genes Supressores de Tumor , Complexo de Golgi/metabolismo , Humanos , Hibridização in Situ Fluorescente , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Mapeamento de Híbridos Radioativos , Transfecção , Células Tumorais Cultivadas
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