Abstract
MicroRNA is a class of noncoding RNAs able to base pair with complementary messenger RNA sequences, inhibiting their expression. These regulatory molecules play important roles in key cellular processes including cell proliferation, differentiation and response to DNA damage; changes in miRNA expression are a common feature of human cancers. To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression. These stages are represented by cell lines derived from normal epithelial (H16N2), atypical ductal hyperplasia (21PT), primary in situ ductal carcinoma (21NT) and pleural effusion of a lung metastasis (21MT-1 and 21MT-2). In a global microRNA expression analysis, miR-205-5p was the only miRNA to display an important downregulation in the metastatic cell lines (21MT-1; 21MT-2) when compared to the non-invasive cells (21PT and 21NT). The lower amounts of miR-205-5p found also correlated with high histological grades biopsies and with higher invasion rates in a Boyden chamber assay. This work pinpoints miR-205-5p as a potential player in breast tumor invasiveness.
Highlights
Breast cancer is the most frequent carcinoma in women and a highly heterogeneous disease
The comparison between all cell lines representing the different stages of tumor progression (21PT, 21NT, 21MT1 and 21MT2) and the cell line obtained from the normal breast tissue (H16N2) revealed a large number of deregulated miRNAs (Fig 1, Figs A-D in S1 File)
The 21T series is composed of five cell lines: H16N2, representative of adjacent non-tumoral breast cells; 21PT, representative of Atypical Ductal Hyperplasia (ADH) cells; 21NT of Ductal Carcinoma in Situ (DCIS) and 21MT1 and 21MT2, of Invasive Metastatic Carcinoma (IMC) [8]
Summary
Breast cancer is the most frequent carcinoma in women and a highly heterogeneous disease. Diagnostic and treatment decision are mainly based on classical biological variables including morphology, tumor grade, presence of lymph-node metastasis and molecular markers [1]. Cancer progression is a multistep process, progressing from normal epithelia to an atypical ductal hyperplasia to ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) culminating in metastasis [2]. The knowledge on the DCIS transition to IDC is still incomplete and there are many questions concerning breast cancer progression.
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