Cytoplasmic alpha-fetoprotein functions as a co-repressor in RA-RAR signaling to promote the growth of human hepatoma Bel 7402 cells.
The role of AFP in the retinoic acid-RAR signaling pathway was investigated in human hepatoma Bel 7402 cells. The results showed that AFP and RAR-beta were co-localized and interacted in cytoplasm. AFP may inhibit translocation of RAR-beta into the nucleus via competitive binding to RAR-beta with ATRA, which was reversed by AFP-siRNA transfection. Our data suggest that the ATRA resistance of Bel 7402 cells is at least in part attributable to their high level of cytoplasmic AFP. Thus, by counteracting the effect of AFP, it may be possible to increase the sensitivity of tumor cells to ATRA.
Li
Mengsen
M
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100083, China.
Li
Hui
H
Li
Chaoying
C
Guo
Liyuan
L
Liu
Han
H
Zhou
Sheng
S
Liu
Xinhua
X
Chen
Zhuo
Z
Shi
Shuanglin
S
Wei
Jiang
J
McNutt
Michael A
MA
Li
Gang
G
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077022:Survivin; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000378:metabolism*
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D018168:Receptors, Retinoic Acid; D000077022:Survivin; D000509:alpha-Fetoproteins; D014212:Tretinoin