MicroRNA expression patterns in precursor lesions and (hereditary) breast cancer

In this thesis we studied the role of microRNAs (miRNA’s) in breast cancer development. Little is known of these recently discovered modulators of protein expression with regard to their role in breast carcinoma development. MicroRNA's (miRNA's) are a subclass of small (18-25 nucleotides in length), non-coding RNAs, which can negatively regulate the expression of proteins at the posttranscriptional level. In some tumors up or down regulation of the expression of miRNA’s and their alleged target genes has been demonstrated. For some miRNA’s the target genes are known for most of the miRNA’s the target genes remain elusive. In chapter 2 we review the literature regarding miRNA expression in breast cancer and its precursors. In chapter 3 we describe the expression of miR-21 using in situ hybridization in 15 cases of FEA and/or DCIS and 17 additional cases with DCIS. We investigated the expression of an additional set of miRNA’s, including miR-145, miR-146a, miR-155, miR-205 and miR-210 in FEA, DCIS and IDC by the miRNA-ISH method.We investigated the expression of an additional set of miRNA’s, including miR-145, miR-146a, miR-155, miR-205 and miR-210 in FEA, DCIS and IDC by the miRNA-ISH method.In chapter we give a short review on hereditary breast carcinoma and its relation with mutations in the BRCA1 gene located on chromosome 17q21 and the BRCA2 gene located on chromosome 13q12-13.In this thesis we have provided data that underline the importance of miRNA’s in cell differentiation and pathogenesis of breast carcinoma. Our study is largely descriptive and the data need confirmation by functional studies. It is clear that microarray and qRT-PCR results needs confirmation by ISH in tissue. Other epigenetic mechanisms regulating protein expression apart from genetic mechanisms must be taken into account. The relation between miRNA expression and protein expression (eventually everything comes down to protein expression) is not clear. MiRNA profiling studies will probably fill part of the gap that exists between RNA profiling and protein expression (~30% of all RNA transcripts is not translated to protein) the effects of miRNA expression and interference must be studied in cell lines.

	Titel en inhoudsopgave
	Hoofdstuk 1
	Hoofdstuk 2
	Hoofdstuk 3
	Hoofdstuk 4
	Hoofdstuk 5
	Hoofdstuk 6
	Engelse samenvatting, discussie en toekomstperspectieven
	Samenvatting
	Chinese samenvatting
	Dankwoord
	Volledige dissertatie

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