Journal Article

Underexpression of transcriptional regulators is common in metastatic breast cancer cells overexpressing Bcl-x<sub>L</sub>

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

in Carcinogenesis

Volume 27, issue 6, pages 1169-1179
Published in print June 2006 | ISSN: 0143-3334
Published online February 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi363
Underexpression of transcriptional regulators is common in metastatic breast cancer cells overexpressing Bcl-xL

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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 α1-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.

Keywords: CP, crossing point; ZFP5, human zinc finger protein 5; i.m.f.p., into the mammary fat pad; PAGE, polyacrylamide gel electrophoresis; STRING, Search Tool for the Retrieval of Interacting Genes/Proteins; SPSS, Statistical Package for the Social Sciences; TBP, TATA-binding protein; TAF-172, TBP-associated factor 172

Journal Article.  7562 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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