Tumor-associated genes differentially expressed in breast tumors regarding the presence or absence of estrogen and progesterone receptors

MA Nagai, PhD, a N Rós, Ms, a EC Miracca, Ms, a RLA Silva, Bsc, b AF Carvalho, Ms b FB Runza, Ms, b LFL Reis, PhD b MM Brentani, PhD, a

a Departamento de Radiologia, Disciplina de Oncologia da Universidade de São Paulo. b Ludwig Institute for Cancer Research, Sao Paulo, Brazil

Increasing body of experimental and clinical data support the involvement of the estrogen on the proliferation of hormone-dependent breast tumors. ER and progesterone receptor (PR), which is regulated by estrogen via ER, has been used as prognostic markers in the clinical management of breast cancer patients. The aim of the present study is to identify tumor-associated genes differentially expressed in breast tumors regarding the presence or absence of ER and PR using cDNA microarrays. cDNAs were synthesized using 30 µg of total RNA from both ER+/PR+ and ER-/PR- breast tumors by RT in the presence of [αP32]dCTP. The labeled cDNAs were denatured and hybridized to cDNA array blots containing duplicates of 1940 tumor-derived and expressed sequence tags (ESTs). The experiments were performed in duplicate and data from each element was acquired by phosphorimage scanning and analyzed by the ArrayVison software (Molecular Dynamics). Several transcripts, such as those encoding tensin, integrin β4, DC24, DC48, heat shock 90KD protein 1 and ubiquitin specific protease 4 were highly expressed in the ER-/PR- breast tumors. In addition to that, transcripts showing homology with hypothetical proteins and several novel transcripts, showing no homology to known genes were detected in increased levels in ER-/PR- or ER+/PR+ tumors. Differences in gene expression profiles are likely to explain the phenotypic differences between hormone-responsive and hormone-unresponsive breast tumors. Further characterization of the novel genes identified in this study and the precise relationship between the altered expression of these genes and breast tumorigenesis are under investigation.

KEY WORDS: breast cancer, steroid receptors, microarrays, .

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.