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국문 초록
췌장암은환자의 5 년평균 생존율에서 9 %의 낮은생존율을 갖는 가장 치명적인 악성 종양 중 하나이다. 췌장암은 종양 간의 높은 이질성으로 인해 돌연변이 특성을 정의 하기 어려운데, 우리는 서로 다른 26 개의 췌장암 세포주를 수립하고 전장 엑솜 시퀀싱 및 RNA
시퀀싱과 western blotting 을 수행하여 각 세포주들의 돌연변이
특성과 단백질 발현량을 확인하고 항암제 반응성을 검사하였다.
췌장암의대표적인것으로알려진 KRAS 코돈 12번돌연변이는 26
개 중 22개의 세포주에서 발견되었으며, 4개의 세포주에서 KRAS 돌연변이가 발견되지 않았다. KRAS 야생형을 가지는 췌장암은
SNU-3752 세포주를 제외하고 대체로 항암제에 낮은 저항성을
가지며 이러한 차이는 단백질 발현량과 서로 다른 유전적 요인에
의한것으로보인다. KRAS 야생형의돌연변이들은 세포외기질의
구성과 분해와 관련된 신호 전달과 관련이 있는 것으로 나타났다.
KRAS 돌연변이 세포주들은 항암제 반응성과 단백질 발현량의
차이를 통해서 높은 종양 이질성을 확인하였으며 KRAS 돌연변이 세포주들에서 trametinib 과 phospho-ERK 1/2 단백질 발현량 간의