All-trans retinoic acid is capable of inducing folate receptor β expression in KG-1 cells.
The high expression of folate receptor (FR) on cancer cells might be a potential target for cancer therapy. In this study, the FR-β expression and the modulation effect of all-trans retinoic acid (ATRA) in a number of cancer cell lines were analyzed. The gateway of ATRA activity on FR-β expression was further studied by a panel of retinoid activators and inhibitors. The results revealed that ATRA was capable of upregulating the expression of FR-β protein in KG-1 cells in a dosage-dependent manner, not in KG-1a, NB4, HL60, 293, L1210, JAR, and Hela cells. FR-β mRNA expression in KG-1 cells was higher when ATRA was present in culture medium at 10⁻⁶ mol/L for 5 days, and it went down to baseline when ATRA was removed from the medium, vice versa. The upregulation of FR-β expression in KG-1 cells by ATRA was not associated with cell proliferation and differentiation. In addition, activators of retinoid acid receptor (RAR)α and RARγ, CD336, and CD2781 also induced FR-β expression. The induction of FR-β expression by CD336 could be inhibited by RARγ antagonist CD2665; RARβ agonist CD-417 and CD-2314 as well as retinoid X receptor (RXR) agonist LG100364 could not induce FR-β expression. These results indicate that ATRA within a certain range of concentration could reversibly induce the expression of FR-β in a dosage- and cell type-dependent manner, and its action in KG-1 cells might be associated with the signal transduction of retinoid receptor RARα and RARγ, rather than RARβ and RXRs.
Xu
Ying
Y
Department of Pediatrics, Clinical Division of Medicine, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, People's Republic of China.
Wang
Tianyou
T
Tang
Ruihong
R
Tang
Suoqin
S
D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D005260:Female; D058976:Folate Receptor 2 / Q000187:drug effects / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology*; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology
D058976:Folate Receptor 2; D058973:Folate Receptors, GPI-Anchored; D014212:Tretinoin