Protein expression of BLM gene and its apoptosis sensitivity in hematopoietic tumor cell strains

Abstract

Patients with Bloom syndrome (BS) show an immunodeficiency, an enhanced sister chromatid exchanges (SCEs), a strong genetic instability and an increased predisposition to all. In order to investigate the differential expression of BLM protein in hematopoietic tumor cell strains and study the effects of BLM gene on ultraviolet (UV)-or hydroxyurea (HU)-induced apoptosis, Western blot was used to detect the expression of BLM protein in normal human bone marrow mononuclear cells and 4 kinds of hematopoietic tumor cell strains. The 4 kinds of hematopoietic tumor cells were exposed to UV light with a germicidal UV lamp or treated with 2 mmol/L hydroxyurea and the apoptotic rate was detected by using AnnexinV-FITC. The results showed that these tumor cells expressed BLM protein higher than the normal human bone marrow mononuclear cells (P<0.01). In the 4 hematopoietic tumor cells, BLM protein was all specially cleaved in response to UV-or HU-induced apoptosis. The increase of BLM protein expression may play an important role in the development of these tumors, and BLM proteolysis is likely to be a general feature of the apoptotic response.

Keywords

BLM gene / protein / apoptosis / hematopoietic tumor cell strains

References

[1] DaviesS. L., NorthP. S., HicksonI. D.. Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Nat Struct Mol Biol, 2007, 14(7): 677-679

[2] SekiM., TadaS., EnomotoT.. Function of recQ family helicase in genome stability. Subcell Biochem, 2006, 40: 49-73

[3] Amor-GuéretM.. Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis. Cancer Lett, 2006, 236(1): 1-12

[4] ImamuraO., FujitaK., ShimamotoA., et al.. Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells. Oncogene, 2001, 20: 1143-1151

[5] HuP., BerestenS. F., BrabantA., et al.. Evidence for BLM and Topoisomerase alpha interaction in genomic stability. Hum Mol Genet, 2001, 10: 1287-1298

[6] KolodnerR. D., PutnamC. D., MyungK.. Maintenance of genome stability in Saccharomyces cerevisiae. Science, 2002, 297: 552-557

[7] FreireR., d’Adda Di FagagnaF., WuL., et al.. Cleavage of the Bloom’s syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase III alpha. Nucleic Acids Res, 2001, 29: 3172-3180

[8] AbabouM., DumaireV., LecluseY., et al.. Cleavage of BLM and sensitivity of Bloom’s syndrome cells to hydroxurea and UVC radiation. Cell Cycle, 2002, 1: 262-266