Underexpression of transcriptional regulators is common in metastatic breast cancer cells overexpressing Bcl-xL.
Carcinogenesis
; 27(6): 1169-79, 2006 Jun.
Article
en En
| MEDLINE
| ID: mdl-16492678
ABSTRACT
Bcl-xL gene induces metastasis in the lung, lymph nodes and bone when breast cancer cells are inoculated in Nude Balb/c mice. In an attempt to identify the molecules required for diverse metastatic foci, we compared gene expression levels in tumor cells and metastatic variants with a cDNA GeneFilter containing 4000 known genes. The transcriptional regulators of alpha1-fetoprotein transcription factor, TBP-associated factor 172 (TAF-172) and the human zinc finger protein 5 (ZFP5) were downregulated. The expression of TAF-172 was inversely proportional to Bcl-xL expression (ANOVA P < 0.0001) and metastatic activity (ANOVA P < 0.0001). A protein interaction program allowed us to functionally associate Bcl-xL and TAF through TATA-binding protein (TBP), suggesting that Bcl-xL connects metabolic pathways with transcriptional machinery. The prediction included proteins involved in apoptosis, electron transfer, kinases and transcription factors. These results indicate that the selection of diverse metastatic cells from the broad spectrum of tumor cell leads to the underexpression of certain transcriptional regulators that might act as adaptor molecules to different microenvironments, and indicate that the synergistic activity of several genes is needed for the selection process in several metastatic foci.
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Bases de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Neoplasias de la Mama
/
Regulación Neoplásica de la Expresión Génica
/
Proteína bcl-X
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Carcinogenesis
Año:
2006
Tipo del documento:
Article
País de afiliación:
España