Notch3 intracellular domain accumulates in HepG2 cell line.
BACKGROUND
By mediating local cell-cell interactions, the Notch signaling pathway seems to control a variety of processes from cell fate decisions during development, to stem cell renewal and to differentiation in many adult tissues. Hence, perturbed Notch signaling may be involved both in the development and the spread of cancer. The expression and the functional role of some major components of the Notch signaling pathway in human hepatocellular carcinoma (HCC) are poorly characterized.


METHODS
Notch3, HES1, Jagged1 and Delta1 were analyzed both at the RNA and protein levels in the HepG2 liver cell line derived from human HCC.


RESULTS
The results of this study demonstrated, for the first time, that both Jagged1 and Delta1 ligands and the downstream effector gene HES1 are expressed in the HepG2 actively proliferating cell line. Moreover, a high expression of Notch3 intracellular domain, indicative of constitutively activated Notch signaling, was the only detectable Notch3 subunit in HepG2.


CONCLUSIONS
These findings suggest that Notch3 may be involved in mechanisms controling the differentiation and the spread of HCC and that Notch3 activation may be dependent on both Jagged1 and Delta 1 ligands.
Giovannini
Catia
C
Department of Internal Medicine and Gastroenterology, University of Bologna and S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy. cgiovannini@aosp.bo.it
Lacchini
Michela
M
Gramantieri
Laura
L
Chieco
Pasquale
P
Bolondi
Luigi
L
D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000096:biosynthesis* / Q000235:genetics; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; C000606273:JAG1 protein, human; C499374:NOTCH3 protein, human; C064045:delta protein; C078493:HES1 protein, human