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유방암 세포주의 세포 외 Cystine 공급 의존성 분석
김도형, MD Abdullah, 육한나, 이승진 忠南大學校 醫藥品開發硏究所 2021 藥學論文集 Vol.36 No.-
Intracellular cysteine is supplied by transsulfuration pathway diverged from methionine cycle or by the reduction of cystine which is uptaken by system xc-. Inhibition of system xc- is expected to be effective anti-cancer strategy in a population of cancer cells which are dependent on extracellular cystine for their growth. This study was aimed to evaluate the dependency of 5 kinds of breast cancer cells on extracellular cystine for proliferation and analyze mRNA expression pattern of 8 enzymes in transsulfuration pathway/methionine cycle in 59 kinds of breast cancer cell lines. Depletion of cystine in me- dia induced cytotoxicity in MDA-MB-468 and MDA-MB-231 cells, whereas delayed growth rate in T47D, SK-BR3, and MCF7 cells. MCF7 cells showed the lowest growth inhibition of 33.2% by cystine depletion, which indicates that transsulfuration might be active. Glycine N-methyltransferase (GNMT) mRNA ex- pression showed negative correlation with SLC7A11 mRNA expression, a catalytic subunit of system xc-(Pearson’s correlation score = -0.513, P < 0.001), but not with cellular cystine dependency. These results showed that cellular phenotype for extracellular cystine dependency is various in breast cancer cell lines. It would be useful to develop biomarker for cellular cystine dependency to identify cancer cell type which would benefit from system xc- targeting.