Down-regulation of CD44 contributes to the differentiation of HL-60 cells induced by ATRA or HMBA.
CD44 is highly expressed in human acute myeloid leukemia (AML) cells. Some experiments had shown that it was possible to reverse differentiation blockage in AML cells by CD44 ligation with specific antibodies, indicating that CD44 was closely related to the differentiation of leukemia cells. The differentiation of acute promyelocytic leukemia cell line HL-60 cells could be induced by all trans-retinoic acid (ATRA) and hexamethylene bisacetamide (HMBA), but so far the mechanism was not demonstrated clearly. In the present study, we investigated whether ATRA or HMBA induced the growth arrest of HL-60 cells by down-regulating the expression of CD44. The results indicated that the proliferation of HL-60 cells was obviously inhibited and the differentiation was induced by both ATRA and HMBA. The decreased expression of CD44 and cyclin E mRNA, and the increased expression of p27 and p21 at mRNA levels were observed. Furthermore, there was a negative correlation between the expression of CD44 and p27. It was concluded that ATRA and HMBA played a role in the differentiation induction of HL-60 cells, which was mediated by the down-regulation of CD44, accompanied by down-regulation of cyclin E, and up-regulation of p27 and p21 mRNA.
Liu
Jianing
J
Department of Hemato-oncology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, China.
Bi
Gaofeng
G
Wen
Pei'e
P
Yang
Weihua
W
Ren
Xia
X
Tang
Tianhua
T
Xie
Chao
C
Dong
Wei
W
Jiang
Guosheng
G
D000081:Acetamides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D018922:HL-60 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
D000081:Acetamides; D000970:Antineoplastic Agents; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D050760:Cyclin-Dependent Kinase Inhibitor p27; D014212:Tretinoin; C014026:hexamethylene bisacetamide