Roles of miRNAs in the switch of TGF-beta from tumor suppressor to pro-oncogenic factor in cancer progression

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCI	CANCER-23

Authors

• Y. Nagano
• M.P. Lee
• L.M. Wakefield

Abstract

TGF-beta is a pleiotropic growth factor that switches from tumor suppressor to pro-oncogenic factor during breast cancer progression. We hypothesize that miRNAs may contribute to the TGF-beta switch, as miRNA expression is deregulated in cancer, and TGF-beta regulates expression and biogenesis of some miRNAs. We used a series of human breast cancer cell lines derived from the MCF10A breast epithelial cell line to model breast cancer progression. TGF-beta is a tumor suppressor in M-I (MCF10A; normal), M-II (premalignant), and M-IIIcl4 (low-grade tumor) lines, whereas TGF-beta promotes metastasis in M-IV line. We compared expression profiles of miRNAs by Next Gen miRNA sequencing 1) basally in cultures of all four cell lines and 2) in M-IIIcl4 and M-IV with and without TGF-beta treatment. We focused on miRNAs whose basal expression level differs between M-IIIcl4 and M-IV since these may contribute to the altered molecular context that drives the TGF-beta switch. 75 miRNAs were differentially expressed by > 1.5 fold between M-IIIcl4 and M-IV. Among these, we selected several miRNAs whose expression was regulated by TGF-beta, then examined whether these miRNAs modulate cellular responses to TGF-beta. The results of the biological assays will be discussed.

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