p53 및 Rb 항암유전자가 HL60 암세포주의 성장과 세포사멸에 미치는 영향

Abstract

Cancer is considered to occur through abnormal growth and differentiation processes, in which oncogenes and tumor suppressor genes are deeply related. Recently, gene transfer with p53 or Rb tumor suppressor gene is expected as a new effective therapeutic strategy in many kinds of cancers. By using retroviral vector system, we transduced p53 or Rb tumor suppressor genes into HL60 promyelocytic leukemia cells, and analysed their growth suppression effects. Titer of p53 retrovirus was 2.0xl05/ml, and that of Rb retrovirus was 6.0xl04/ml when NIH3T3 cells were used as target cells. HL60 leukemic cells infected with p53 retroviruses showed growth inhibitions in normal RPMI-1640 media. But they died rapidly in media containing chemotherapeutic agent, 75% of them died within 4 days and all of them died within 9 days of exposing chemotherapeutic agent. Their DNAs were extracted and electrophoresed in agarose gel, and we identified DNA ladders characteristic of apoptotic cell death. HL60 cells infected with Rb retroviruses showed growth inhibitions and no apoptotic signs in media containing chemotherapeutic agent. These findings suggest that retroviral vector mediated p53 or Rb tumor suppressor gene transfer into cancer cells can suppress tumor cell growth effectively in leukemic cells; and by using both p53 gene transfer and chemotherapy, leukemic cell apoptosis can be induced effectively. Key Words: p53, Rb, Retroviral vector, HL60, Apoptosis