In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4615-4615
Abstract:
Purpose: We have reported that SF3B1 gene mutations are rare in colorectal cancer patients and SF3B1 gene mutations in codon 1074 are responsible for resistance to SF3B1 inhibitor (FR901464, FR) at the AACR annual meeting 2013. SF3B1 gene mutations in hematological malignancies are considered to be related to tumor progression. To elucidate the influence by SF3B1 gene mutation in colorectal cancer, we assessed the tumor growth of colorectal cancer cells bearing SF3B1 gene mutation in vitro and in vivo. ExperimentalDesign: We assessed the tumor growth in vitro and in vivo using FR resistant clones (DLD/FR1, DLD/FR2, DLD/FR3, HCT/FR1, HCT/FR2, and LoVo/FR1) derived from DLD1, HCT116, and LoVo. We also performed microarray analysis of DLD1, DLD/FR1, HCT116, and HCT/FR1 with or without FR for 24 h to compare the change of gene expression by FR or SF3B1 gene mutation. Results: Doubling time of growth in DLD/FR1, DLD/FR2, HCT/FR1, and HCT/FR2 in vitro was same as their parental cells. However, doubling time of growth in DLD/FR3 and LoVo/FR1 in vitro was longer than their parental cells. In mouse subcutaneous xenograft models, the tumor volume of DLD1/FR1, HCT/FR1, and HCT/FR2 were 61%, 32 %, and 25%, to compared to that of their parental DLD1 or HCT116 one month after inoculation, respectively. Microarray analysis showed the genes and pathways affected by SF3B1 inhibitor and SF3B1 gene mutation did not match at all. Though SF3B1 inhibitor strongly inhibited pathways related to cell cycle, Fanconi anemia, homologous recombination, ubiquitin mediated proteolysis, nucleotide excision repair, oocyte meiosis, basal transcription factors, and endocytosis, SF3B1 gene mutation did not influence these pathways. The genes influenced by SF3B1 gene mutations included MHC class I/II, MHC MYC, BCL2, IL2, and IL10. Conclusion: Our data indicated SF3B1 gene mutation in colorectal cancer induced disadvantage in cancer progression by the different pathway from SF3B1 inhibitor. Citation Format: Tomoki Yamano, Shuji Kubo, Nagahide Matsubara, Aya Yano, Naohiro Tomita. Influence of SF3B1 gene mutation is different from that of Sf3B1 inhibitor in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4615. doi:10.1158/1538-7445.AM2014-4615
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-4615
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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