Expression of Notch1 and Jagged1 proteins in acute myeloid leukemia cells.
Cell fate of hematopoietic progenitors is regulated by interaction between Notch proteins on progenitors and Notch ligands such as Jagged1 on stromal cells. Since acute myeloid leukemia (AML) originates from dysregulated hematopoietic progenitors, some abnormalities in the Notch-Jagged system may exist in AML cells. As the first step to clarify this, we examined the expression of Notch1 and Jagged1 proteins in eight AML cell lines and 15 fresh AML samples by immunoblotting. In the Notch1 protein, two bands, a 300 kDa band and a 120 kDa band, which appeared to be a full-length protein and a transmembrane fragment, respectively, were recognized in five AML cell lines and six fresh samples. In addition, three of the five cell lines showed a 110 kDa fragment, which appeared to be from an intracellular domain, namely an active form. One cell line showed aberrant sized fragments, which suggested a structural abnormality. Jagged1 protein was recognized in six cell lines and six fresh samples. In four cell lines and four fresh samples, both Notch1 and Jagged1 proteins were observed. In these cells, Notch1 and Jagged1 proteins may interact among themselves. We showed that Notch1 and Jagged1 proteins are widely expressed in AML cells. We hypothesize that some abnormalities in the Notch-Jagged system which cause the excessive self-renewal and the block of differentiation, may be involved in the abnormal proliferation of AML cells.
Tohda
S
S
Department of Laboratory Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan. tohda.mlab@tmd.ac.jp
Nara
N
N
D000208:Acute Disease; D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011499:Protein Processing, Post-Translational; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D014157:Transcription Factors