Involvement of Annexin V in Antiproliferative Effects of Gonadotropin-Releasing Hormone Agonists on Human Endometrial Cancer Cell Line

Shibata, Satoshi; Sato, Hírokazu; Ota, Hirotaka; Karube, Akihiro; Takahashi, Osamu; Tanaka, Toshinobu

doi:10.1006/gyno.1997.4746

Cited by 22 publications

(13 citation statements)

References 13 publications

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“…Annexin V, also known as calphobindin I, has been shown to be an endogenous inhibitor of protein kinase C, a key enzyme in cellular signal transduction. The inhibition of protein kinase C by annexin V is presumed to be ultimately related to carcinogenesis and studies have demonstrated that a decrease in the production of annexin V may lead to the dysregulated activation of protein kinase C [32,33]. Accordingly, the decrease in annexin V was postulated to be involved in disorders of cell differentiation, proliferation, and carcinogenesis.…”

Section: Cancer-related Proteinsmentioning

confidence: 99%

Two-dimensional electrophoresis map of the human hepatocellular carcinoma cell line, HCC-M, and identification of the separated proteins by mass spectrometry

et al. 2000

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Section: Cancer-related Proteinsmentioning

confidence: 99%

Two-dimensional electrophoresis map of the human hepatocellular carcinoma cell line, HCC-M, and identification of the separated proteins by mass spectrometry

et al. 2000

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“…The presence of the LHRH receptor has prompted many researchers to investigate agonists and antagonists of LHRH-R and study the responses in multiple tumors. In a majority of cases, receptor suppression caused inhibition of cellular proliferation [31,32]. LHRH agonists have been used clinically in the treatment of prostate, breast and gynecological cancers and have produced excellent clinical results [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

LHRH receptor expression in sarcomas of bone and soft tissue

Deivaraju¹,

Temple²,

Block³

et al. 2016

Hormone Molecular Biology and Clinical Investigation

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Aim: Luteinizing hormone releasing hormone (LHRH) is a neurohormone, secreted by the hypothalamus, which regulates the secretion of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary. LHRH acts by binding to receptors located in the pituitary gland. These receptors (LHRH receptors) have also been found in the cytoplasm of many tumor cells that involve both the reproductive and non-reproductive organs. These receptors have been demonstrated in prostate and breast cancers, endometrial carcinomas, renal cell carcinoma, lymphoma, carcinoma of liver, pancreas and skin. So far, the expression of LHRH receptors on sarcomas (i.e. malignant tumors of mesenchymal origin) has not been studied, except for endometrial sarcomas. It has also been demonstrated that both LHRH agonists and antagonists can down-regulate these receptors and thus inhibit these tumor cells. Another major therapeutic implication is that these receptors can be targeted specifically by peptides conjugated to anti-cancer drugs. The purpose of this study was to determine if LHRH receptors are expressed in primary and/or metastatic sarcomas of human origin. Methods: We looked at LHRH receptor expression in 38 consecutive sarcoma specimens, using immunohistochemistry. The specimens were either from office biopsy or from resected tumor; these were confirmed as sarcomas by histopathological examination. The receptor staining characteristics and the staining intensity were also documented. The pattern of staining was classified either as "focal or diffuse staining of the cytoplasm" and the intensity of staining was graded on a scale from 1+ to 4+. Results: Positive receptor staining was seen in 25 of the 38 (66%) specimens. Twelve of the specimens stained diffusely and 13 had focally positive staining. Three tumors had 1+ staining, 10 had 2+ staining, six had 3+ staining, and six tumors had 4+ staining. The tumors included undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, myofibroblastic sarcoma, myxofibrosarcoma, liposarcoma, dermatofibrosarcoma protuberans, metastatic chondrosarcoma and chordoma. Conclusion: Sarcomas express LHRH receptors with a varying incidence and degree. Our study suggests that those sarcomas that are LHRH receptor positive could potentially be treated with targeted chemotherapy.

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“…The in vitro proliferation of a variety of human tumor cell lines, including those from ovarian cancers can be inhibited by GnRH-I and its agonistic analogs in a dose- and time-dependent manner [4,9,11,12,17-20]. In most human ovarian cancer cells except for the ovarian cancer cell line EFO-27 GnRH-I antagonists act like agonists indicating that the dichotomy of GnRH-I agonists and antagonists does not exist in tumor cells [5,9].…”

Section: The Gnrh-i System In Human Ovarian Cancersmentioning

confidence: 99%

Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer

Gründker

Emons

2003

Reprod Biol Endocrinol

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The expression of GnRH (GnRH-I, LHRH) and its receptor as a part of an autocrine regulatory system of cell proliferation has been demonstrated in a number of human malignant tumors, including cancers of the ovary. The proliferation of human ovarian cancer cell lines is time- and dose-dependently reduced by GnRH and its superagonistic analogs. The classical GnRH receptor signal-transduction mechanisms, known to operate in the pituitary, are not involved in the mediation of antiproliferative effects of GnRH analogs in these cancer cells. The GnRH receptor rather interacts with the mitogenic signal transduction of growth-factor receptors and related oncogene products associated with tyrosine kinase activity via activation of a phosphotyrosine phosphatase resulting in downregulation of cancer cell proliferation. In addition GnRH activates nucleus factor κB (NFκB) and protects the cancer cells from apoptosis. Furthermore GnRH induces activation of the c-Jun N-terminal kinase/activator protein-1 (JNK/AP-1) pathway independent of the known AP-1 activators, protein kinase (PKC) or mitogen activated protein kinase (MAPK/ERK).Recently it was shown that human ovarian cancer cells express a putative second GnRH receptor specific for GnRH type II (GnRH-II). The proliferation of these cells is dose- and time-dependently reduced by GnRH-II in a greater extent than by GnRH-I (GnRH, LHRH) superagonists. In previous studies we have demonstrated that in ovarian cancer cell lines except for the EFO-27 cell line GnRH-I antagonist Cetrorelix has comparable antiproliferative effects as GnRH-I agonists indicating that the dichotomy of GnRH-I agonists and antagonists might not apply to the GnRH-I system in cancer cells. After GnRH-I receptor knock down the antiproliferative effects of GnRH-I agonist Triptorelin were abrogated while the effects of GnRH-I antagonist Cetrorelix and GnRH-II were still existing. In addition, in the ovarian cancer cell line EFO-27 GnRH-I receptor but not putative GnRH-II receptor expression was found. These data suggest that in ovarian cancer cells the antiproliferative effects of GnRH-I antagonist Cetrorelix and GnRH-II are not mediated through the GnRH-I receptor.

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Involvement of Annexin V in Antiproliferative Effects of Gonadotropin-Releasing Hormone Agonists on Human Endometrial Cancer Cell Line

Cited by 22 publications

References 13 publications

Two-dimensional electrophoresis map of the human hepatocellular carcinoma cell line, HCC-M, and identification of the separated proteins by mass spectrometry

Two-dimensional electrophoresis map of the human hepatocellular carcinoma cell line, HCC-M, and identification of the separated proteins by mass spectrometry

LHRH receptor expression in sarcomas of bone and soft tissue

Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer

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