Abstract
Splice variants (SV) of receptors for growth hormone-releasing hormone (GHRH) have been found in several human cancer cell lines. GHRH antagonists inhibit growth of various human cancers, including osteosarcomas and Ewing's sarcoma, xenografted into nude mice or cultured in vitro and their antiproliferative action could be mediated, in part, through these SV of GHRH receptors. In this study, we found mRNA for the SV1 isoform of GHRH receptors in human osteosarcoma line MNNG/HOS and SK-ES-1 Ewing's sarcoma line. We also detected mRNA for GHRH, which is apparently translated into the GHRH peptide and secreted by the cells, as shown by the presence of GHRH-like immunoreactivity in the conditioned media of cell cultures. In proliferation studies in vitro, the growth of SK-ES-1 and MNNG/HOS cells was dose-dependently inhibited by GHRH antagonist JV-1-38 and an antiserum against human GHRH. Our study indicates the presence of an autocrine stimulatory loop based on GHRH and SV1 of GHRH receptors in human sarcomas. The direct antiproliferative effects of GHRH antagonists on malignant bone tumors appear to be exerted through the SV1 of GHRH receptors on tumoral cells.
| Original language | English |
|---|---|
| Pages (from-to) | 47-53 |
| Number of pages | 7 |
| Journal | Regulatory Peptides |
| Volume | 108 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Oct 15 2002 |
| Externally published | Yes |
Fingerprint
Keywords
- Anticancer drugs
- Autocrine growth factors
- GHRH
- GHRH antagonists
- GHRH receptors
- Human malignant bone tumors
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
- Neuroscience(all)
Cite this
Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors. / Busto, R.; Schally, Andrew V; Braczkowski, R.; Plonowski, A.; Krupa, M.; Groot, K.; Armatis, P.; Varga, J. L.
In: Regulatory Peptides, Vol. 108, No. 2-3, 15.10.2002, p. 47-53.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors
AU - Busto, R.
AU - Schally, Andrew V
AU - Braczkowski, R.
AU - Plonowski, A.
AU - Krupa, M.
AU - Groot, K.
AU - Armatis, P.
AU - Varga, J. L.
PY - 2002/10/15
Y1 - 2002/10/15
N2 - Splice variants (SV) of receptors for growth hormone-releasing hormone (GHRH) have been found in several human cancer cell lines. GHRH antagonists inhibit growth of various human cancers, including osteosarcomas and Ewing's sarcoma, xenografted into nude mice or cultured in vitro and their antiproliferative action could be mediated, in part, through these SV of GHRH receptors. In this study, we found mRNA for the SV1 isoform of GHRH receptors in human osteosarcoma line MNNG/HOS and SK-ES-1 Ewing's sarcoma line. We also detected mRNA for GHRH, which is apparently translated into the GHRH peptide and secreted by the cells, as shown by the presence of GHRH-like immunoreactivity in the conditioned media of cell cultures. In proliferation studies in vitro, the growth of SK-ES-1 and MNNG/HOS cells was dose-dependently inhibited by GHRH antagonist JV-1-38 and an antiserum against human GHRH. Our study indicates the presence of an autocrine stimulatory loop based on GHRH and SV1 of GHRH receptors in human sarcomas. The direct antiproliferative effects of GHRH antagonists on malignant bone tumors appear to be exerted through the SV1 of GHRH receptors on tumoral cells.
AB - Splice variants (SV) of receptors for growth hormone-releasing hormone (GHRH) have been found in several human cancer cell lines. GHRH antagonists inhibit growth of various human cancers, including osteosarcomas and Ewing's sarcoma, xenografted into nude mice or cultured in vitro and their antiproliferative action could be mediated, in part, through these SV of GHRH receptors. In this study, we found mRNA for the SV1 isoform of GHRH receptors in human osteosarcoma line MNNG/HOS and SK-ES-1 Ewing's sarcoma line. We also detected mRNA for GHRH, which is apparently translated into the GHRH peptide and secreted by the cells, as shown by the presence of GHRH-like immunoreactivity in the conditioned media of cell cultures. In proliferation studies in vitro, the growth of SK-ES-1 and MNNG/HOS cells was dose-dependently inhibited by GHRH antagonist JV-1-38 and an antiserum against human GHRH. Our study indicates the presence of an autocrine stimulatory loop based on GHRH and SV1 of GHRH receptors in human sarcomas. The direct antiproliferative effects of GHRH antagonists on malignant bone tumors appear to be exerted through the SV1 of GHRH receptors on tumoral cells.
KW - Anticancer drugs
KW - Autocrine growth factors
KW - GHRH
KW - GHRH antagonists
KW - GHRH receptors
KW - Human malignant bone tumors
UR - http://www.scopus.com/inward/record.url?scp=0037107433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037107433&partnerID=8YFLogxK
U2 - 10.1016/S0167-0115(02)00109-X
DO - 10.1016/S0167-0115(02)00109-X
M3 - Article
VL - 108
SP - 47
EP - 53
JO - Regulatory Peptides
JF - Regulatory Peptides
SN - 0167-0115
IS - 2-3
ER -