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Carcinogenesis Advance Access published online on February 20, 2006
Carcinogenesis, doi:10.1093/carcin/bgi363
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received August 19, 2005
Revised December 19, 2005
Accepted February 1, 2006

CANCER BIOLOGY

Under-expression of transcriptional regulators is common in metastatic breast cancer cells overexpressing Bcl-xL

Olga Méndez 1, Berta Martín 1, Rebeca Sanz 1, Ramón Aragüés 2, Victor Moreno 3, Baldo Oliva 2, Verena Stresing 1, and Angels Sierra 1 *

1 Centre d'Oncologia Molecular, Institut de Recerca Oncológica, IDIBELL, Hospital Duran i Reynals, Gran Via s/n, Km 2,7, L'Hospitalet Ll, 08907, Spain
2 Grup de Bioinformàtica Estructural (GRIB-IMIM), Universitat Pompeu Fabra, C/ Doctor Aiguader, 80, Barcelona 08003, Catalonia, Spain
3 Servei d'Epidemiologia Institut Català d'Oncologia, Hospital Duran i Reynals, Gran Via s/n, Km 2,7, L'Hospitalet Ll, 08907, Spain

* To whom correspondence should be addressed.
Angels Sierra, E-mail: asierra{at}iro.es


  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 {alpha}1-fetoprotein transcription factor, TBP-associated factor 172 (TAF-172), and the human zinc finger protein 5 (ZFP5) were down-regulated. 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 TBP proteins 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 under-expression 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.

Keywords: Apoptosis; Bc-xL; Breast Cancer; Genomics; Metastasis; TBP-associated factor.
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