Expression of growth hormone–releasing hormone receptor splice variant 1 in primary human melanomas

Chatzistamou, Ioulia; Volakaki, Aspasia Athina; Schally, Andrew V.; Kiaris, Hippokratis; Kittas, Christos

doi:10.1016/j.regpep.2007.12.008

Cited by 19 publications

(18 citation statements)

References 23 publications

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“…Because SV1 acts as a membrane receptor, in a manner analogous to that of GHRH receptor, our findings may be attributable to SV1 activation by other peptides that share structural similarities with GHRH, such as the vasoactive intestinal peptide and pituitary adenylcyclase activating polypeptide. It is noteworthy that cytoplasmic immunohistochemical expression has also been observed in other neoplasms (18,19). We were able to demonstrate that SV-1 was present in most of our cases.…”

Section: Discussionsupporting

confidence: 77%

“…The incidence of colon cancer is increased in persons with acromegaly, suggesting that excessive secretion of GH or IGF-I may be a contributing factor in this disease (8). GHRH antagonists can inhibit tumor growth indirectly through suppression of the endocrine GH-IGF-I axis and also by direct action on the tumor cells expressing SV-1 (7,(14)(15)(16)(17)(18)(19). The indirect mechanism is important for those cancers that depend on IGF-I as a growth factor.…”

Section: Discussionmentioning

confidence: 99%

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The Immunohistochemical Expression of Growth Hormone-Releasing Hormone Receptor Splice Variant 1 Is a Favorable Prognostic Marker in Colorectal Cancer

Theophanous

Petraki

Scorilas

et al. 2009

Mol Med

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Hypothalamic growth hormone (GH)-releasing hormone (GHRH) regulates the release of GH from the pituitary gland. The receptors for GHRH (GHRH-R) are expressed predominantly in the pituitary. Recent evidence demonstrates that splice variants of the GHRH receptor are also expressed in several nonpituitary tissues, both normal and tumoral, as well as in cancer cell lines. The aim of this study was to investigate the expression of the splice variant 1 (SV-1) of GHRH-R in colorectal cancer (CRC). Seventy patients who underwent partial colectomy for CRC were enrolled in the study. Immunohistochemical expression of SV-1 was studied in paraffin-embedded sections of patient tumor tissue. A cytoplasmic supranuclear expression of SV-1 was observed in CRC as well as in the normal colon mucosa. Tumor grade and pathological stage were negatively correlated with expression of SV-1 (P = 0.012 and P = 0.013, respectively). CRCs metastatic to the liver showed a lower expression of SV-1 than did primary tumors, but this difference was not statistically significant. Kaplan-Meier and Cox univariate survival analyses indicated an improved survival time in patients with high SV-1 compared with those with low GHRH-R expression, but this difference was not statistically significant. The immunohistochemical expression of SV-1 seems to be a favorable prognostic factor in CRC.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

The Immunohistochemical Expression of Growth Hormone-Releasing Hormone Receptor Splice Variant 1 Is a Favorable Prognostic Marker in Colorectal Cancer

Theophanous

Petraki

Scorilas

et al. 2009

Mol Med

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“…This finding can further support the theories that, on certain cancer cells and tumors, SV1 functions as the main therapeutic target, 32 and in melanomas has a crucial role in the progression of the disease. 22 The exposure of A375 cells to MIA-690 altered the subcellular localization of p27, an event that is, at least in part, responsible for the observed changes in cell cycle progression. In many cancers the level of p27 is reduced in the nucleus, and cytoplasmic p27 appears to acquire a cell cycle-independent oncogenic function to promote cancer cell invasion.…”

Section: Discussionmentioning

confidence: 98%

“…It has recently been reported that the SV1 receptor is involved in the pathogenesis of melanomas demonstrating that the progression from a state of dysplasia into malignancy is accompanied by expression of SV1 receptor. 22 We have shown previously that GHRH antagonists inhibit the growth of diverse human tumors xenografted into nude mice. [23][24][25][26][27][28][29][30] Many of these published studies reported the effects of early-stage GHRH antagonists that were later considered unsuitable for clinical development due to limited stability or low potency.…”

Section: Introductionmentioning

confidence: 98%

Novel GHRH antagonists suppress the growth of human malignant melanoma by restoring nuclear p27 function

et al. 2014

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Malignant melanoma is the deadliest form of skin cancer; the treatment of advanced and recurrent forms remains a challenge. It has recently been reported that growth hormone-releasing hormone (GHRH) receptor is involved in the pathogenesis of melanoma. Therefore, we investigated the effects of our new GHRH antagonists on a human melanoma cancer cell line. Antiproliferative effects of GHRH antagonists, MIA-602, MIA-606 and MIA-690, on the human melanoma cell line, A-375, were studied in vitro using the MTS assay. The effect of MIA-690 (5 mg/day 28 d) was further evaluated in vivo in nude mice bearing xenografts of A-375. Subcellular localization of p27 was detected with Western blot and immunofluorescent staining. MIA-690 inhibited the proliferation of A-375 cells in a dose-dependent manner (33% at 10 mM, and 19.2% at 5 mM, P < 0 .05 vs. control), and suppressed the growth of xenografted tumors by 70.45% (P < 0.05). Flow cytometric analysis of cell cycle effects following the administration of MIA-690 revealed a decrease in the number of cells in G2/M phase (from 19.7% to 12.9%, P < 0.001). Additionally, Western blot and immunofluorescent studies showed that exposure of A-375 cells to MIA-690 triggered the nuclear accumulation of p27. MIA-690 inhibited tumor growth in vitro and in vivo, and increased the translocation of p27 into the nucleus thus inhibiting progression of the cell cycle. Our findings indicate that patients with malignant melanoma could benefit from treatment regimens, which combine existing chemotherapy agents and novel GHRH-antagonists.

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“…Moreover, in vitro studies utilizing human oestrogenindependent breast cancer cell lines (MDA-MB-468 and MDA-MB-435), as well as mouse mammary carcinomas, showed that GHRH antagonists can directly inhibit cell proliferation [119,120]. Thus, an antagonist of GHRH-R might be effective in the treatment of some oestrogen-independent cancers, and it might be desirable to selectively target the SV1 isoform, potentially sparing normal GHRH-R function [48,49,121]. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 F o r R e v i e w O n l y express the full-length pGHRH-R and its splice variants [44].…”

Section: Alternative Splicing Of Gpcrs In Cancermentioning

confidence: 99%

Alternative splicing of G protein-coupled receptors: physiology and pathophysiology

Markovic

Challiss

2009

Cell. Mol. Life Sci.

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Abstract. The G protein-coupled receptors (GPCRs) are a superfamily of transmembrane receptors that have a broad distribution and can collectively recognize a diverse array of ligands. Activation or inhibition of GPCR signalling can affect many (patho)physiological processes and consequently they are a major target for existing and emerging drug therapies.A common observation has been that the pharmacological, signalling and regulatory properties of GPCRs can vary in a cell-and tissue-specific manner. Such "phenotypic" diversity might be attributable to post-translational modifications and/or association of GPCRs with accessory proteins, however, post-transcriptional mechanisms are also likely to contribute. Although, approximately 50% of GPCR genes are intronless, those that possess introns can undergo alternative splicing, generating GPCR subtype isoforms that may differ in their pharmacological, signalling and regulatory properties. In this Review we shall highlight recent research into GPCR splice-variation, and discuss the potential consequences this might have for GPCR function in health and disease.

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Expression of growth hormone–releasing hormone receptor splice variant 1 in primary human melanomas

Cited by 19 publications

References 23 publications

The Immunohistochemical Expression of Growth Hormone-Releasing Hormone Receptor Splice Variant 1 Is a Favorable Prognostic Marker in Colorectal Cancer

The Immunohistochemical Expression of Growth Hormone-Releasing Hormone Receptor Splice Variant 1 Is a Favorable Prognostic Marker in Colorectal Cancer

Novel GHRH antagonists suppress the growth of human malignant melanoma by restoring nuclear p27 function

Alternative splicing of G protein-coupled receptors: physiology and pathophysiology

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