Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers

Peptides ◽  
2002 ◽  
Vol 23 (6) ◽  
pp. 1127-1133 ◽  
Author(s):  
Artur Plonowski ◽  
Andrew V Schally ◽  
Rebeca Busto ◽  
Magdalena Krupa ◽  
Jozsef L Varga ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Splice Variants ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Prostate Cancers

scholarly journals Splice variant of growth hormone-releasing hormone receptor drives esophageal squamous cell carcinoma conferring a therapeutic target

2020 ◽  
Vol 117 (12) ◽  
pp. 6726-6732 ◽  
Author(s):  
Xiao Xiong ◽  
Xiurong Ke ◽  
Lu Wang ◽  
Zhimeng Yao ◽  
Yi Guo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Splice Variant ◽  
Splice Variants ◽  
Glycolytic Enzyme ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone

The extrahypothalamic growth hormone-releasing hormone (GHRH) and its cognate receptors (GHRH-Rs) and splice variants are expressed in a variety of cancers. It has been shown that the pituitary type of GHRH-R (pGHRH-R) mediates the inhibition of tumor growth induced by GHRH-R antagonists. However, GHRH-R antagonists can also suppress some cancers that do not express pGHRH-R, yet the underlying mechanisms have not been determined. Here, using human esophageal squamous cell carcinoma (ESCC) as a model, we were able to reveal that SV1, a known splice variant of GHRH-R, is responsible for the inhibition induced by GHRH-R antagonist MIA-602. We demonstrated that GHRH-R splice variant 1 (SV1) is a hypoxia-driven promoter of tumor progression. Hypoxia-elevated SV1 activates a key glycolytic enzyme, muscle-type phosphofructokinase (PFKM), through the nuclear factor kappa B (NF-κB) pathway, which enhances glycolytic metabolism and promotes progression of ESCC. The malignant actions induced by the SV1–NF-κB–PFKM pathway could be reversed by MIA-602. Altogether, our studies demonstrate a mechanism by which GHRH-R antagonists target SV1. Our findings suggest that SV1 is a hypoxia-induced oncogenic promoter which can be an alternative target of GHRH-R antagonists.

scholarly journals Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Human Prostate Cancer

2002 ◽  
Vol 87 (10) ◽  
pp. 4707-4714 ◽  
Author(s):  
Gabor Halmos ◽  
Andrew V. Schally ◽  
Tamas Czompoly ◽  
Magdalena Krupa ◽  
Jozsef L. Varga ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Hormone ◽  
Splice Variants ◽  
Human Prostate ◽  
Growth Hormone Releasing Hormone ◽  
Human Prostate Cancer ◽  
Releasing Hormone
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