Triple-negative breast cancers express receptors for luteinizing hormone-releasing hormone (LHRH) and respond to LHRH antagonist cetrorelix with growth inhibition.
The aim of the present study was to evaluate the expression of receptors for luteinizing hormone-releasing hormone (LHRH) in human specimens of triple-negative breast cancers (TNBC). In addition, we used in vitro and in vivo models of TNBC to investigate if these receptors are suitable targets for the treatment with the LHRH antagonist cetrorelix. Receptors for LHRH were expressed in all tumor samples and in the TNBC cell lines HCC1806 and HCC1937. The proliferation of both TNBC cell lines was significantly inhibited in vitro by 1 microM cetrorelix. Injections of 3 mg cetrorelix on day 1 and 21 resulted in a significant growth inhibition of HCC1806 tumors xenografted into nude mice. Tumors of mice treated with cetrorelix expressed less mRNA for EGFR and HER3 receptors than untreated tumors. After treatment of cells with Cetrorelix a flow cytometric analysis of the cell cycle revealed a decrease in S-phase. Given the low toxicity and clinical availability of cetrorelix, this peptide antagonist should be considered for phase II studies in patients with advanced TNBC.
Buchholz
Stefan
S
The Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center and South Florida VA Foundation for Research and Education, Miami, FL 33125, USA.
Seitz
Stephan
S
Schally
Andrew V
AV
Engel
Jörg B
JB
Rick
Ferenc G
FG
Szalontay
Luca
L
Hohla
Florian
F
Krishan
Awtar
A
Papadia
Andrea
A
Gaiser
Timo
T
Brockhoff
Gero
G
Ortmann
Olaf
O
Diedrich
Klaus
K
Köster
Frank
F
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D020893:Receptor, ErbB-3 / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D007987:Gonadotropin-Releasing Hormone; D006727:Hormone Antagonists; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D011960:Receptors, Estrogen; D011966:Receptors, LHRH; D011980:Receptors, Progesterone; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C062876:cetrorelix