Roles of Disabled-2 gene on hematopoietic cell differentiation and BCR-ABL signaling

• Main Author: 陳淑鑫
• Other Authors: Ching-Ping Tseng
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/58401563944994498542

碩士 === 長庚大學 === 基礎醫學研究所 === 90 === Disabled 2 (DAB2) is a potential tumor suppressor gene with a growth inhibitory effect on several cancer types. We have recently shown that the expression of DAB2 was induced at the protein and mRNA levels upon TPA mediated megakaryocyte differentiation of human chronic myeloid leukemia K562 cells, a BCR-ABL positive cell line (Tseng et al., 2001). To understand the role of DAB2 in the proliferation and differentiation, we examined the effects of cell growth rate, morphology and cell cycle distribution in K562 cell by DAB2 expression. The role of DAB2 in modulating BCR-ABL signal transduction pathways was also determinded. Our results indicate that a slightly increase in G2/M cell fractions when expressed Dab2 cDNA. Thus, we used western blot to characterize the expression of G2/M phase regulatory proteins, including RB, cyclinA, cyclinB, cdc2 and RBBP. However, we observed neither those proteins nor the cell growth rate and morphology changed when DAB2 presented. In examining the role of DAB2 in modulating BCR-ABL signal transduction pathways, co-immunoprecipitation was used to determine whether DAB2 associates with GRB2 and BCR-ABL. We found that DAB2 interacted with BCR-ABL and enhanced the interaction between GRB2 and BCR-ABL. In contrast, expressions of the N-terminal, C-terminal deletion mutant and S24A mutant of DAB2 had no effect on the interaction between GRB2 and BCR-ABL. Take together, our results indicate that DAB2 may lead to modulate of BCR-ABL signaling.