Expression of retinoic acid receptor mRNA in hematopoietic cells.
Retinoic acid (RA) has profound effects upon the proliferation and differentiation of many hematopoietic cells. The mechanism by which RA acts is unclear. Recently, several retinoic acid receptors (RAR) have been cloned. We studied expression of RAR-alpha mRNA by RNA blots in hematopoietic cells blocked at different stages of differentiation. All hematopoietic cells expressed RAR-alpha mRNA (3.4, 4.5 kb) including KG-1 (myeloblasts); HL-60 (promyelocytes); ML3, THP-1, U937 (myelomonoblasts and monoblasts); K562 (erythroblasts); and S-LB1 (T-lymphocytes). In addition, transformed cells from four non-hematopoietic tissues also expressed RAR-alpha mRNA. Steady-state levels of RAR-alpha mRNA were not affected by induction of terminal differentiation of HL-60 cells to either granulocytes or macrophages. Furthermore, both actively proliferating and resting lymphocytes from the same individuals expressed equal concentrations of RAR-alpha mRNA. Taken together, data suggest that level of expression of RAR-alpha mRNA is not related to cellular proliferation. We also showed that exposure to ligand (all-trans retinoic acid) did not change levels of RAR-alpha mRNA in three different cell types. Half-life of RAR-alpha mRNA was short (0.7 h) as determined by measuring decay of message after addition of actinomycin D. Consistent with this finding, accumulation of RAR-alpha mRNA increased in cells of three lines as their protein synthesis was inhibited. In summary, hematopoietic cells of different lineages and stages of differentiation constitutively express RAR-alpha mRNA. This expression is unaffected either by terminal differentiation or cell cycle. The RAR-alpha mRNA is short-lived and super-inducible by a protein synthesis inhibitor.
Kizaki
M
M
UCLA Department of Medicine 90024.
Koeffler
H P
HP
Lin
C W
CW
Miller
C W
CW
D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D006207:Half-Life; D006412:Hematopoietic Stem Cells / Q000032:analysis*; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D008214:Lymphocytes / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis*; D018168:Receptors, Retinoic Acid
D002352:Carrier Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D003513:Cycloheximide