SETD1A Pharmaceutical composition for preventing or treating anticancer drug resistant breast cancers comprising expression or activity inhibitor of SETD1A as an active ingredient
The present invention relates to a pharmaceutical composition for the prophylactic or therapeutic treatment of cancer-resistant breast cancer containing, as an active ingredient, an expression or activity inhibitor of SETD1A (SET domain containing 1A), which is one of enzymes for methylating histone H3 lysine position 4 in human cells Specifically, it was confirmed that SETD1A was overexpressed in breast cancer cells compared to normal breast cells. When SETD1A was overexpressed in breast cancer cells and regulated specific gene expression induced by estrogen receptor in breast cancer cells and decreased expression of SETD1A in cells, It was confirmed that the proliferation of breast cancer cell lines was inhibited and cell apoptosis was significantly induced and cell migration was reduced. When tamoxifen was treated with cells and expression of SETD1A was decreased, It was found that the inhibition of cancer cell proliferation, cell suicide induction, and cell migration inhibition were increased In addition, when the expression of SETD1A was inhibited in breast cancer cells having tamoxifen resistance, it was confirmed that cell proliferation was remarkably inhibited. Thus, the composition containing the SETD1A expression or activity inhibitor of the present invention as an active ingredient, For the treatment of <； / RTI >；본 발명은 인체 세포에서 히스톤(histone) H3 라이신 4번 위치를 메틸화 하는 효소 중 하나인 SETD1A(SET domain containing 1A)의 발현 또는 활성 억제제를 유효성분으로 함유하는 항암제 내성 유방암의 예방 또는 치료용 약학적 조성물에 관한 것으로, 구체적으로 SETD1A가 정상 유방 세포에 비해 유방암 세포에서 과발현 되어 있음을 확인하였고, 유방암 세포에서 에스트로겐 수용체로 유도되는 특이적인 유전자 발현을 조절하며, 세포 내 SETD1A의 발현을 감소시켰을 때, 유방암 세포주의 증식이 억제되며, 세포자살(apoptosis)이 현저하게 유도되고, 세포 이동(cell migration)이 감소됨을 확인하였으며, 타목시펜(tamoxifen)을 세포에 처리하고, SETD1A의 발현을 감소시켰을 때, 타목시펜 단독 처리시보다 암 세포의 증식 억제, 세포자살 유도, 및 세포 이동 억제 효과가 증가함을 확인하였고, 또한, 타목시펜 내성을 갖는 유방암 세포에서 SETD1A의 발현을 억제하였을 때, 세포 증식이 현저하게 억제됨을 확인하여, 본 발명의 SETD1A의 발현 또는 활성 억제제를 유효성분으로 함유하는 조성물은 항암제 내성 유방암의 치료를 위해 유용하게 사용될 수 있다.
