Polycomb genes in breast carcinomas. Regulation and expression analysis

Abstract

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We examine the RNA expression of three Polycomb group (PcG) members, Bmi-1, Mel-18 and Hpc-2, and their possible relationship in a large series of breast carcinomas to investigate the role of these transcriptional repressors in human breast carcinogenesis. Moreover, a correlation study between expression levels and several clinical pathological parameters of the tumors was designed, with the objective of appraising the prognostic value of these expressions. The PcG proteins regulate gene activity at the chromatin level. Together with the counteracting Trithorax group (TrxG) proteins, PcG proteins act as a memory system that ensures the faithful transmission of cell identities throughout cell division. PcG complexes are transcriptional repressors of several genes related to cell-cycle control and proliferation, implying PcG proteins in tumor development. Deregulation of mammalian PcG members such as Bmi-1, Mel-18 and Hpc-2 has recently been found to be involved in carcinogenesis. As PcG regulation has been described in established cell lines and cell-culture experiments, our task will be to find support for the in vivo relevance of the in vitro findings. We quantified the RNA expression of Bmi-1, Mel-18 and Hpc-2 by RT-PCR in a series of 89 breast carcinomas and correlated the data with several clinical pathological parameters of the tumors. Bmi-1, Mel-18 and Hpc-2 were differently expressed in the tumors, though the overexpression of Bmi-1 was the most frequent alteration detected (25.8%). In addition, concomitant behavior in the regulation of the three PcG members was detected and had statistical significance (p < 0.01). Finally, deregulation of Bmi-1, Mel-18 and Hpc-2 was associated with poor prognosis for clinical pathological parameters, such as positive steroid receptors. In conclusion, our study of primary breast carcinomas indicates that the PcG members, Bmi-1, Mel-18 and Hpc-2, are differently expressed in breast tumors and behave in a similar way in the regulation of their expressions. In general, deregulation of the three genes was associated with poor prognostic clinical pathological parameters, and so may be available prognostic markers in the analysis of breast carcinogenesis.