Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P10415 (
Bcl-2
)
33,771
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The acidic (leucine-rich) nuclear phosphoprotein 32 family member B (
ANP32B
), a highly conserved member of the acidic nuclear phosphoprotein 32 (ANP32) family, is critical for the development of normal tissue. However, its role in the development of hepatocellular carcinoma (HCC) is controversial. In this study, we elucidated the role of
ANP32B
in HCC cell lines and tissues.
ANP32B
expression in HCC cell lines was modulated using siRNA and
ANP32B
expression plasmids and lentiviruses. The levels of apoptosis-related proteins were analyzed by real-time RT-PCR and Western blotting. The expression of
ANP32B
in tissues from patients with HCC was investigated using real-time RT-PCR and immunohistochemistry.
ANP32B
knockdown by siRNA altered the expression of apoptosis-related proteins in HCC cell lines and reduced the expression of cleaved forms of caspase 3 and caspase 9, but not that of caspase 8, in HCC cells cultured with the pro-apoptotic agent staurosporine. Phosphorylated Bad was upregulated, whereas Bak was downregulated. Moreover, ABT-737, which binds to and inhibits anti-apoptotic proteins of the
Bcl-2
family, rendered HCC cells resistant to apoptosis induced by
ANP32B
silencing. Conversely,
ANP32B
overexpression decreased Bad phosphorylation and upregulated Bak, but did not induce apoptosis because Bax expression was downregulated. In tissues from patients with HCC, a low tumor/non-tumor ratio of
ANP32B
mRNA expression was related to advanced UICC stage (p = 0.032). TUNEL-positive cells were observed in parallel with
ANP32B
expression in HCC tissues.
ANP32B
modulates Bad phosphorylation as well as Bak and Bax expression, resulting in regulation of apoptosis in HCC. These findings indicate the potential value of
ANP32B
as a therapeutic target for HCC.
...
PMID:Downregulation of ANP32B exerts anti-apoptotic effects in hepatocellular carcinoma. 2848 57
