Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition

Köster, Frank; Engel, Jörg B.; Schally, Andrew V.; Hönig, Arnd; Schröer, Andreas; Seitz, Stephan; Hohla, Florian; Ortmann, O.; Diedrich, K.; Buchholz, Stefan

doi:10.1007/s10549-008-0120-4

Cited by 30 publications

(39 citation statements)

References 45 publications

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“…1A and B, and Table I). Our results are in line with previous reports on the presence of pGHRH-R and SV1 on breast cancer cell lines (11,26). We determined that the concentration at which cellular growth was inhibited by 30% (IC 30 ) was 1 µM and hereafter used this concentration in subsequent experiments.…”

Section: Discussionsupporting

confidence: 91%

“…The proliferation of the two cell lines, MDAMB435 and T47D, expressing only SV1 receptors, was inhibited to a lesser degree than that in cells positive for both the pGHRH-R plus SV-1 cells, however the difference was not significant. These results support the previous findings that GHRH antagonists can exert their antiproliferative effects on tumors and cell lines, even when the pGHRH-R cannot be detected and only the SV-type receptors are present (11,36). The role of GHRH in the promotion of proliferation and prevention of apoptosis in cancer cells is well known (34,37).…”

Section: Discussionsupporting

confidence: 91%

“…Earlier reports have shown that GHRH antagonists decrease cell viability of breast cancers in vitro (9)(10)(11) and inhibit the growth and metastases of orthotopic breast cancer models in vivo (8,16). Previously, we demonstrated that GHRH antagonists induce cell death through the major apoptotic pathways and by a membrane destabilizing effect on the mitochondrial membrane potential in two glioblastoma cell lines (22).…”

Section: Introductionmentioning

confidence: 74%

“…Antagonistic analogues of growth hormone releasinghormone (GHRH), developed in our laboratory, have been shown to inhibit the growth of various cancers (6)(7)(8)(9)(10)(11), through indirect and direct pathways (6). Thus, GHRH antagonists can suppress tumor growth indirectly by blocking GH release from the pituitary and consequently the hepatic production of IGF-I (6,12), which is an established mitogen for various cancers (13), is likewise inhibited.…”

Section: Introductionmentioning

confidence: 99%

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The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines

et al. 2011

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Abstract. Growth hormone releasing hormone (GHRH) antagonists have been developed for the treatment of various cancers. We investigated the effects of a novel GHRH antagonist, MIA-602, on nine breast cancer cell lines, differing in their expression for estrogen-, progesterone-and HER-2 receptors. We detected the presence of pituitary-type GHRH receptors (pGHRH-R) on 6 of the 9 breast cancer cell lines. The main splice variant of pGHRH-R, SV1, was found on all 9 cell lines. MTT assay showed that following treatment with MIA-602, cell viability decreased significantly in all 9 cell lines. The reduction in cell viability was greater in cells positive for both pGHRH-R and SV1, than in cells positive for only SV1, but the difference was not significant. Using Western blotting, we demonstrated that the levels of phosphoAkt, -GSK3β and -ERK1/2 decreased significantly following exposure to MIA-602 and the level of phospho-p38 increased after treatment. The reduction of the phosphorylated antiapoptotic proteins was significantly greater in cells where both pGHRH-R and SV1 were present, than where only SV1 was expressed. In conclusion, our study shows that MIA-602 is effective against a wide range of breast cancer cells in vitro, independently of their receptor positivity, suggesting the potential use of GHRH antagonists also in the treatment of triple-negative breast cancer. The effect of MIA-602 was mediated nearly as well in tumors that expressed only the SV1 receptor compared to those in which both SV1 and pGHRH-R were present, although a difference could be detected at the level of cell signaling.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines

et al. 2011

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“…Gene expression analysis has identified molecular classes of breast cancer that are biologically and clinically distinct (1). One of these subgroups, which has attracted significant attention in recent years, is triple-negative breast cancer (TNBC).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Hedgehog signaling molecules and its involvement in triple-negative breast cancer

et al. 2011

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Abstract. The purpose of this study was to investigate the activation of Hedgehog (Hh) signaling molecules and its involvement in triple-negative breast cancer (TNBC). A total of 123 cases of paraffin blocks, including 83 cases of primary breast carcinoma, 30 cases of mammary hyperplasia and 10 cases of normal breast tissue, were immunohistochemically analyzed for Sonic Hedgehog (SHH), Patched-1 (PTCH1), Smoothened (SMO) and glioma-associated oncogene homoglog 1 (GLI1) expression. The expression of SMO and GLI1 in TNBC was significantly increased in comparison to non-triple-negative breast cancer (nTNBC). GLI1 expression manifested an inverse association with the estrogen receptor. The levels of GLI1 expression were increased in lymph nodepositive cases. The expression of SHH and SMO was increased in high histological grades. Furthermore, the expression of SMO and GLI1 was correlated with superior tumor stage. The expression of SHH, SMO and GLI1 was significantly increased in breast cancer and mammary hyperplasia. PTCH1 expression was significantly decreased in breast cancer compared to mammary hyperplasia and normal breast tissue. For the first time, clinical evidence has been provided in support of significant roles of Hh signaling in TNBC. Hh signaling is involved in breast ductal changes and malignant transformation. Measures to inhibit Hh activity may improve the prognosis of TNBC patients.

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3-D High-Resolution Mapping of the Heterogeneity in Mitochondrial Redox State of Human Breast Tumor Xenografts

Nioka

Chance

et al. 2011

Advances in Experimental Medicine and Biology

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Triple-negative breast cancers express receptors for growth hormone-releasing hormone (GHRH) and respond to GHRH antagonists with growth inhibition

Cited by 30 publications

References 45 publications

The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines

The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines

Overexpression of Hedgehog signaling molecules and its involvement in triple-negative breast cancer

3-D High-Resolution Mapping of the Heterogeneity in Mitochondrial Redox State of Human Breast Tumor Xenografts

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