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Contents

Abstract 5

1. Introduction 7

2. Materials and methods 10

Cell culture 10

Flow Cytometry 10

Western blot analysis 11

Immunofluorescence 12

3. Result 14

Selection of breast cancer cell lines for experiment 14

Neuregulin-1 induces increase of CD44-positive CSC fraction. 15

Neuregulin-1 induces expression of CSC markers. 17

4. Discussion 19

5. Reference 23

Figure 29

초록보기

 In breast cancer, neuregulin-1 is known as a ligand for the HER3 receptor, which has no intrinsic tyrosine kinase activity. Activated Her3 receptor by neuregulin-1 binding forms heterodimer with other Her receptor family and mediates downstream signaling pathways, leading to multiple effects, including growth, proliferation, decreased apoptosis, cellular migration, and angiogenesis.

Cancer stem cell (CSC), a subgroup of cancer cell, is considered to have features of stem cells such as self-renewal ability and pluripotent differentiation into other types of mature cell. CSCs and their relation to the tumor recurrence, metastasis, and chemo-resistance draw attention in these days.

This study showed that neuregulin-1 treatment induces CSC characteristics in breast cancer cell lines. Using breast cancer cell lines such as MCF7, SKBr3, MDA-MB 468, changes related to the CSC characteristics were analyzed. In MCF7 and SKBr3 cells, increase of CSC fraction and expression of CSC markers were observed after neuregulin-1 treatment. However, MDA-MB 468 cells showed intrinsic high expression of CSC markers and high cellular fraction of CSCs. In MDA-MB 468 cells, neuregulin-1 treatment made no significant change in CSC characteristics. The result implies a presence of mechanism by which the activated Her receptors by neuregulin-1 contribute to acquire the CSC-like characteristics in some types of breast cancer.

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