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Inhibition of Triple Negative Breast Cancer Metastasis by Methionine Restriction
메티오닌 제한이 나타내는 삼중음성 유방암 세포의 전이 억제 효능

DC Field Value Language
dc.contributor.advisor이기원-
dc.contributor.author정혜인-
dc.date.accessioned2017-07-14T06:43:54Z-
dc.date.available2017-07-14T06:43:54Z-
dc.date.issued2015-02-
dc.identifier.other000000025788-
dc.identifier.urihttps://hdl.handle.net/10371/125894-
dc.description학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2015. 2. 이기원.-
dc.description.abstractNutrient deprivation strategies have been proposed as an adjuvant therapy for cancer cells due to their increased metabolic demand. Herein, I examined the specific inhibitory effects of amino acid deprivation on the metastatic phenotypes of the human TNBC lines MDA-MB231 and Hs 578T cells, as well as the orthotopic 4T1 mouse TNBC tumor model. Of the essential amino acids tested, methionine deprivation elicited the strongest inhibitory effects on the migration and invasion of these cancer cells. Methionine deprivation reduced the phosphorylation of focal adhesion kinase (FAK), as well as the activity and mRNA expression of matrix metalloproteinases MMP-2 and MMP-9, two major markers of metastasis, while increasing the mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in MDA-MB-231 cells. Furthermore, methionine restriction downregulated the metastasis-related factor urokinase plasminogen activatior (uPA) and upregulated plasminogen activator inhibitor 1 (PAI-1) mRNA expression. For the in vivo lung metastasis model, female BALB/c mouse were injected into the tail vein with 4T1 mouse TNBC cells and fed on a control diet, 0.1% methionine-containing diet, or a methionine-deprived diet. Animals on the methionine-deprived diet showed lower metastasis rates compared to mice on the control diet. Taken together, these results suggest that methionine deprivation has an inhibitory effect on the migration and invasion of TNBC cells, as well as lung metastasis in BALB/c mouse. Methionine restriction could therefore represent a potential nutritional strategy for more effective cancer therapy.-
dc.description.tableofcontentsCONTENTS

ABSTRACT……………………………………………………………i
CONTENTS………………………………………………………….iii
Ⅰ. INTRODUCTION………………………………………………..1
Ⅱ. MATERIALS AND METHODS………………………………...5
1. Reagents.………………………………………………………5
2. Cell Culture………………………………………………….11
3. Migration assay……………………………………………...11
4. Invasion assay………………………………………………..12
5. Cell viability assay…………………………………………...13
6. Western blot analysis………………………………………..14
7. Gelatin zymography…………………………………………15
8. Real-time quantitative PCR ………………………………..16
9. Animals……………………………………………………… 18
10. In vivo lung metastasis experiments………………………19
11. Statistical analysis …………………………………………20

Ⅲ. RESULTS………………………………………………………...21
1. Methionine deprivation inhibits cell migration and invasion of MDA-MB-231 and Hs 578T cells ………………………..21
2. Methionine deprivation has no significant effect on cell
viability of MDA-MB-231, Hs 578T, or MCF 10A cells……28
3. Methionine deprivation suppresses FAK phosphorylation and activity, in addition to mRNA expression of MMP-2 and MMP-9 in MDA-MB-231 cells ……………………………..31
4. Methionine deprivation inhibits cell migration and invasion in 4T1 cells …………………………………………………..34
5. Methionine deprivation reduces lung metastasis of 4T1 cells in BALB/c mice………………………………………………37
Ⅳ. DISCUSSION……………………………………………………40
Ⅴ. REFERENCES…………………………………………………..44
Ⅵ. 국문 초록………………………………………………………. 47
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dc.formatapplication/pdf-
dc.format.extent1361611 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectMethionine-
dc.subjectMet-
dc.subjectTriple Negative Breast Cancer-
dc.subjectTNBC-
dc.subjectMigration-
dc.subjectInvasion-
dc.subjectMetastasis-
dc.subject.ddc630-
dc.titleInhibition of Triple Negative Breast Cancer Metastasis by Methionine Restriction-
dc.title.alternative메티오닌 제한이 나타내는 삼중음성 유방암 세포의 전이 억제 효능-
dc.typeThesis-
dc.contributor.AlternativeAuthorHyein Jeong-
dc.description.degreeMaster-
dc.citation.pagesiv, 48-
dc.contributor.affiliation농업생명과학대학 농생명공학부-
dc.date.awarded2015-02-
Appears in Collections:
College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Agricultural Biotechnology (농생명공학부)Theses (Master's Degree_농생명공학부)
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