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: EC:2.7.13.3 (
histidine kinase
)
2,405
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although the incidence of de novo neuroendocrine prostate cancer (PC) is rare, recent data suggest that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine hallmarks and androgen receptor (AR) suppression in PC. Previous clinical reports indicate that PCs with a phenotype similar to neuroendocrine tumors can be more amenable to imaging by
18
F-FDG than by PSMA-targeting radioligands. In this study, we evaluated the association between neuroendocrine gene signature and
18
F-FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported
18
F-FDG avidity of PSMA-suppressed tumors.
Methods:
Data-mining approaches, cell lines, and patient-derived xenograft models were used to study the levels of 14 members of the
SLC2A
family (encoding GLUT proteins), 4 members of the hexokinase family (genes
HK1
-
HK3
and
GCK
), and PSMA (
FOLH1
gene) after AR inhibition and in correlation with neuroendocrine hallmarks. Also, we characterize a neuroendocrine-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no neuroendocrine histopathology. We measured glucose uptake in a neuroendocrine-induced in vitro model and a zebrafish model by nonradioactive imaging of glucose uptake using a fluorescent glucose bioprobe,
GB2
-Cy3.
Results:
This work demonstrated that a neuroendocrine gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of
GCK
(encoding glucokinase protein) and decreased expression of
SLC2A12
correlated with earlier biochemical recurrence. In tumors treated with AR inhibitors, high expression of
GCK
and low expression of
SLC2A12
correlated with neuroendocrine histopathology and PSMA gene suppression. GLUT12 suppression and upregulation of glucokinase were observed in neuroendocrine-induced PC cell lines and patient-derived xenograft models. A higher glucose uptake was confirmed in low-PSMA tumors using a
GB2
-Cy3 probe in a zebrafish model.
Conclusion:
A neuroendocrine gene signature in neuroendocrine PC and NELPC associates with a distinct transcriptional profile of GLUTs and hexokinases. PSMA suppression correlates with GLUT12 suppression and glucokinase upregulation. Alteration of
18
F-FDG uptake-associated genes correlated positively with higher glucose uptake in AR- and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient preclinical method for monitoring nonradioactive glucose uptake.
...
PMID:Differential Expression of Glucose Transporters and Hexokinases in Prostate Cancer with a Neuroendocrine Gene Signature: A Mechanistic Perspective for
18
F-FDG Imaging of PSMA-Suppressed Tumors. 3180 71
