TY - JOUR
T1 - Inhibition of growth and metastases of MDA-MB-435 human estrogen-independent breast cancers by an antagonist of growth hormone-releasing hormone
AU - Chatzistamou, Ioulia
AU - Schally, Andrew V.
AU - Varga, Jozsef L.
AU - Groot, Kate
AU - Busto, Rebeca
AU - Armatis, Patricia
AU - Halmos, Gabor
PY - 2001/11/7
Y1 - 2001/11/7
N2 - Antagonists of growth hormone-releasing hormone (GH-RH) inhibit the growth of various cancers by mechanism(s) that include the suppression of the insulin-like growth factors (IGF)-I and/or -II. In this study, nude mice bearing orthotopic implants of MDA-MB-435 human estrogen-independent breast carcinoma received 39 days of therapy with GH-RH antagonist JV-1-36 (20 μg/day). The treatment significantly inhibited tumor growth by 71.1% (p<0.01) and nullified the metastatic potential of MDA-MB-435 cells. Four of eight control mice (50%) developed metastases in the lymph nodes and one (12.5%) in the lung, but none of the animals receiving JV-1-36 showed metastatic spread. GH-RH antagonist JV-1-36 inhibited the growth of MDA-MB-435 cells in vitro, while IGF-I stimulated it. However, mRNA for IGF-I or -II was not detected in MDA-MB-435 cells, indicating that the suppression of autocrine IGFs may not be involved in the antiproliferative mechanism. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-polymerase chain reaction revealed the expression of mRNA for GH-RH receptor splice variant-1 in MDA-MB-435 tumors. Our results suggest that the antitumorigenic action of GH-RH antagonists on MDA-MB-435 breast cancer could be direct and mediated by tumoral GH-RH receptors.
AB - Antagonists of growth hormone-releasing hormone (GH-RH) inhibit the growth of various cancers by mechanism(s) that include the suppression of the insulin-like growth factors (IGF)-I and/or -II. In this study, nude mice bearing orthotopic implants of MDA-MB-435 human estrogen-independent breast carcinoma received 39 days of therapy with GH-RH antagonist JV-1-36 (20 μg/day). The treatment significantly inhibited tumor growth by 71.1% (p<0.01) and nullified the metastatic potential of MDA-MB-435 cells. Four of eight control mice (50%) developed metastases in the lymph nodes and one (12.5%) in the lung, but none of the animals receiving JV-1-36 showed metastatic spread. GH-RH antagonist JV-1-36 inhibited the growth of MDA-MB-435 cells in vitro, while IGF-I stimulated it. However, mRNA for IGF-I or -II was not detected in MDA-MB-435 cells, indicating that the suppression of autocrine IGFs may not be involved in the antiproliferative mechanism. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-polymerase chain reaction revealed the expression of mRNA for GH-RH receptor splice variant-1 in MDA-MB-435 tumors. Our results suggest that the antitumorigenic action of GH-RH antagonists on MDA-MB-435 breast cancer could be direct and mediated by tumoral GH-RH receptors.
KW - Breast cancer therapy
KW - Growth hormone-releasing hormone antagonists
KW - Growth hormone-releasing hormone receptor
KW - Insulin-like growth factors
UR - http://www.scopus.com/inward/record.url?scp=0034772891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034772891&partnerID=8YFLogxK
U2 - 10.1097/00001813-200110000-00008
DO - 10.1097/00001813-200110000-00008
M3 - Article
C2 - 11593058
AN - SCOPUS:0034772891
VL - 12
SP - 761
EP - 768
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
SN - 0959-4973
IS - 9
ER -