title: [Regulation of all-trans retinoic acid and arsenic trioxide on CD44v6 expression in NB4 cells].
abstract: The adhesion molecule CD44 variant isoform (CD44v6) closely associates with progress of acute myeloid leukemia (AML). This study was purposed to investigate the effects of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) on the expression of CD44v6 and the associated signal pathway phosphatidylinositol 3-kinase (PI3K)/Akt in acute promyelocytic leukemia (APL) cell line NB4 cells. The differentiation of NB4 was detected by morphologic observation and flow cytometry; the NB4 cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI double staining; the CD44v6 mRNA expression in NB4 cells was determined by real-time RT-PCR, the CD44v6 protein expression and changes of PI3K/Akt signal pathway in NB4 cells were analysed by Western blot. The results demonstrated that in ATRA-induced differentiation, the transcriptional level of CD44v6 was dominantly down-regulated, the translational level of CD44v6 did not change and the PI3K/Akt signal axis was activated. In As2O3-induced apoptosis, both the transcriptional level and translational level of CD44v6 were remarkably reduced, and the PI3K/Akt pathway was inhibited. It is concluded that the regulation of ATRA on expression of CD44v6 in NB4 cells differs from that of As2O3. The results provide an experimental basis to reveal the different mechanism of ATRA and As2O3 in view of the intercommunication between leukemia cells and hematopoietic microenvironment.
authors.affiliation: Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Huang
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.forename: Zhen-Xing
authors.initials: ZX
authors.lastname: Lin
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Yuan-Zhong
authors.initials: YZ
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; C112697:CD44v6 antigen; D018960:Hyaluronan Receptors; D010087:Oxides; D014212:Tretinoin; D000077237:Arsenic Trioxide