MicroRNA-Expression während der Brustentwicklung und in Mammakarzinomen

Abstract

Profiling studies have identified specific miRNA signatures in hematological and solid malignancies, including breast cancer. This article reviews miRNA expression patterns in breast development and breast cancer focusing on two own previous studies. The first study characterized miRNA expression during postnatal mouse mammary gland development and the second study assessed intratumoral heterogeneity of miRNA expression in breast cancer.In mouse mammary glands the expression of 318 murine miRNAs was analyzed by bead-based flow-cytometric profiling throughout a 16-point developmental time course to derive a comprehensive tissue-specific miRNA expression profile. During breast development 102 miRNAs were expressed in 7 temporally coregulated clusters, which were significantly enriched for miRNA family members and breast cancer-associated miRNAs. None of the investigated single miRNAs or miRNA clusters were exclusively associated with a particular developmental stage.In human breast cancer the expression of 4 candidate miRNAs (miR-10b, miR-210, miR-31 and miR-335) was assessed by quantitative RT-PCR in 132 paraffin-embedded samples of 16 large primary invasive breast cancers including different tumor zones (peripheral, intermediate and central) as well as several axillary lymph node metastases from the same patient. The expression of all four miRNAs showed considerable intratumoral heterogeneity with a mean coefficient of variation of 40 % within the primary tumor and 40 % between different lymph node metastases from the same patient. In comparison, the variation among different patients showed a mean coefficient of variation of 80 % for primary tumors and 103 % for lymph node metastases. Intratumoral heterogeneity can lead to significant sampling bias and multiple areas of the primary tumor or several tumor-involved lymph nodes should be sampled when assessing miRNA profiles as prognostic or predictive biomarkers.