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Molecular transformation of non-tumorigenic MCF10A cells caused by direct contacts with breast cancer cells. : 유방암세포와의 직접접촉을 통해 유도되는 MCF10A 세포주의 분자생물학적 변화
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- Authors
- Advisor
- 노동영
- Major
- 의과대학 협동과정 종양생물학전공
- Issue Date
- 2017-02
- Publisher
- 서울대학교 대학원
- Keywords
- Breast cancer ; MCF10A
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 종양생물학전공, 2017. 2. 노동영.
- Abstract
- The effect of epithelial cancer cells on the adjacent normal epithelial cells has not been investigated clearly. In this study, we hypothesized that the normal mammary epithelial cells can undergo molecular transformation due to the paracrine effects exerted by the adjacent cancer cells. To test the hypothesis, we used both direct and indirect co-culture methods for human mammary epithelial cells and breast cancer cells. MCF10A normal mammary epithelial cells and MDA-MB-231 breast cancer cells were used. MDA-MB-231 cells had minimal effects on MCF10A cells in the indirect co-culture systems. However, when MCF10A cells were grown in direct co-culture system, where the direct contacts between the cancer cells and normal cells were allowed, the cells underwent substantial phenotypic changes. Direct co-culture with MDA-MB-231 cells enhanced MCF10A cells capacity in cell proliferation, colony formation, and migration. Also, cells showed increased expression of various EMT-related markers. The dynamic interactions between the cancer cells and normal cells in the direct co-culture system via cell projections and extracellular vesicles were observed in the live cell imaging assays. To find specific genes and pathways involved in this phenomenon, we performed a phosphorylation assay and RNA sequencing analysis. In phosphorylation assay, phospho-p53 (S392, S46, S15 residue) level was reduced in direct co-cultured MCF10A. Global gene expression profiles of mono-cultured MCF10A cells versus co-cultured MCF10A cells showed downregulation of some keratin genes and upregulation of S100A8 and S100A9. Our findings suggest that MDA-MB-231 cells may disrupt the cell cycle regulation and suppress the expression of E-cadherin in MCF10A cells through upregulation of S100A8/A9 and downregulation of p53 by physical contact and vesicular transport. Future study is needed to find specific pathways which is involved in S100A8/9 and p53.
- Language
- Korean
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