ArticleProceedings of the National Academy of Sciences of the United States of America2000
Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 177 citations in OpenAlex.
- The Role of Splicing Machinery as a Promising Potential Therapeutic Target for Pituitary Neuroendocrine Tumors (PitNETs).Cancers · 2026Review
- Hormone-Driven Growth Signaling as a Therapeutic Target in Acute Myeloid Leukemia: Implications for Drug-Resistant Disease.Journal of personalized medicine · 2026Review
- The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders.Reviews in endocrine & metabolic disorders · 2025Review
- GHRH in diabetes and metabolism.Reviews in endocrine & metabolic disorders · 2025Review
- GHRH and the prostate.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone-releasing hormone receptor (GHRH-R) and its signaling.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone - releasing hormone in the immune system.Reviews in endocrine & metabolic disorders · 2025Review
- GHRH and reproductive systems: Mechanisms, functions, and clinical implications.Reviews in endocrine & metabolic disorders · 2025Review
- Effects of GHRH and its analogues on the Vascular System.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone-releasing hormone and cancer.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone-releasing hormone and its analogues in health and disease.Nature reviews. Endocrinology · 2025Review
- Identification of Small-Molecule Antagonists Targeting the Growth Hormone Releasing Hormone Receptor (GHRHR).Journal of chemical information and modeling · 2024Article
- Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in a Cohort of Hungarian Pediatric Patients with Hematological and Oncological Disorders: A Pilot Study.International journal of molecular sciences · 2024Article
- Growth hormone - releasing hormone in the context of inflammation and redox biology.Frontiers in immunology · 2024Article
- The Role of Receptor-Ligand Interaction in Somatostatin Signaling Pathways: Implications for Neuroendocrine Tumors.Cancers · 2023Review
- Molecular basis of signal transduction mediated by the human GIPR splice variants.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Primary Human Endometrial Carcinomas: Novel Therapeutic Approaches.Molecules (Basel, Switzerland) · 2022Article
- Modulating effects of RAMPs on signaling profiles of the glucagon receptor family.Acta pharmaceutica Sinica. B · 2022Article
- Constitutive signal bias mediated by the human GHRHR splice variant 1.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proliferation of various tumors is inhibited by the antagonists of growth hormone-releasing hormone (GHRH) in vitro and in vivo, but the receptors mediating the effects of GHRH antagonists have not been identified so far. Using an approach based on PCR, we detected two major splice variants (SVs) of mRNA for human GHRH receptor (GHRH-R) in human cancer cell lines, including LNCaP prostatic, MiaPaCa-2 pancreatic, MDA-MB-468 breast, OV-1063 ovarian, and H-69 small-cell lung carcinomas. In addition, high-affinity, low-capacity binding sites for GHRH antagonists were found on the membranes of cancer cell lines such as MiaPaCa-2 that are negative for the vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptor (VPAC-R) or lines such as LNCaP that are positive for VPAC-R. Sequence analysis of cDNAs revealed that the first three exons in SV(1) and SV(2) are replaced by a fragment of retained intron 3 having a new putative in-frame start codon. The rest of the coding region of SV(1) is identical to that of human pituitary GHRH-R, whereas in SV(2) exon 7 is spliced out, resulting in a 1-nt upstream frameshift, which leads to a premature stop codon in exon 8. The intronic sequence may encode a distinct 25-aa fragment of the N-terminal extracellular domain, which could serve as a proposed signal peptide. The continuation of the deduced protein sequence coded by exons 4-13 in SV(1) is identical to that of pituitary GHRH-R. SV(2) may encode a GHRH-R isoform truncated after the second transmembrane domain. Thus SVs of GHRH-Rs have now been identified in human extrapituitary cells. The findings support the view that distinct receptors are expressed on human cancer cells, which may mediate the antiproliferative effect of GHRH antagonists.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.