Triple-negative breast cancers express receptors for luteinizing hormone-releasing hormone (LHRH) and respond to LHRH antagonist Cetrorelix with growth inhibition

被引：41

作者：

Buchholz, Stefan ^{[2
,3
,4
,6
]}

Seitz, Stephan ^{[2
,3
,4
,6
]}

Schally, Andrew V. ^{[2
,3
,4
,5
]}

Engel, Joerg B. ^{[7
]}

Rick, Ferenc G. ^{[2
,3
,4
]}

Szalontay, Luca ^{[2
,3
,4
]}

Hohla, Florian ^{[2
,3
,4
,8
]}

Krishan, Awtar ^{[4
]}

Papadia, Andrea ^{[9
]}

Gaiser, Timo ^{[10
]}

Brockhoff, Gero ^{[6
]}

Ortmann, Olaf ^{[6
]}

Diedrich, Klaus ^{[1
]}

Koester, Frank ^{[1
]}

机构：

[1] Univ Lubeck, Dept Gynecol & Obstet, D-23538 Lubeck, Germany

[2] Vet Affairs Med Ctr, Inst Endocrine Polypeptide & Canc, Miami, FL 33125 USA

[3] S Florida VA Fdn Res & Educ, Miami, FL 33125 USA

[4] Univ Miami, Dept Pathol, Div Hematol Oncol, Miller Sch Med, Miami, FL 33136 USA

[5] Univ Miami, Dept Med, Div Hematol Oncol, Miller Sch Med, Miami, FL 33136 USA

[6] Univ Regensburg, Dept Gynecol & Obstet, D-93053 Regensburg, Germany

[7] Med Univ Wurzburg, Dept Gynecol & Obstet, D-97080 Wurzburg, Germany

[8] Paracelsus Med Univ Salzburg, Dept Internal Med, Gen Hosp Oberndorf, Teaching Hosp, A-5110 Oberndorf, Austria

[9] UM Sylvester Comprehens Canc Ctr, Dept Obstet & Gynecol, Miami, FL 33136 USA

[10] Med Univ Heidelberg, Dept Neuropathol, D-69120 Heidelberg, Germany

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2009年 / 35卷 / 04期

关键词：

triple-negative breast cancer; LHRH antagonist; LHRH receptor; xenografted mouse model; cell cycle analysis; HIGH-AFFINITY BINDING; OVARIAN-CANCER; CELL-LINES; GNRH AGONISTS; NUDE-MICE; ANALOGS; RH; THERAPY; CARCINOMA; MARKERS;

D O I：

10.3892/ijo_00000391

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 I mu M Cetrorelix. Injections of 3 mg Cetrorelix on day I 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.

引用

页码：789 / 796

页数：8

共 37 条

[1]

Bajo AM, 2003, CLIN CANCER RES, V9, P3742

[2]

BAJUSZ S, 1988, INT J PEPT PROT RES, V32, P425

[3] Descriptive analysis of estrogen receptor (ER)negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype - A population-based study from the California Cancer Registry [J].

Bauer, Katrina R. ;

Brown, Monica ;

Cress, Rosemary D. ;

Parise, Carol A. ;

Caggiano, Vincent .

CANCER, 2007, 109 (09) :1721-1728

[4] The triple negative paradox: Primary tumor chemosensitivity of breast cancer subtypes [J].

Carey, Lisa A. ;

Dees, E. Claire ;

Sawyer, Lynda ;

Gatti, Lisa ;

Moore, Dominic T. ;

Collichio, Frances ;

Ollila, David W. ;

Sartor, Carolyn I. ;

Graham, Mark L. ;

Perou, Charles M. .

CLINICAL CANCER RESEARCH, 2007, 13 (08) :2329-2334

[5] Triple-negative breast cancer: Clinical features and patterns of recurrence [J].

Dent, Rebecca ;

Trudeau, Maureen ;

Pritchard, Kathleen I. ;

Hanna, Wedad M. ;

Kahn, Harriet K. ;

Sawka, Carol A. ;

Lickley, Lavina A. ;

Rawlinson, Ellen ;

Sun, Ping ;

Narod, Steven A. .

CLINICAL CANCER RESEARCH, 2007, 13 (15) :4429-4434

[6]

Dondi D, 2006, ONCOL REP, V15, P393

[7] GONADOTROPIN-RELEASING-HORMONE (GNRH)-BINDING SITES IN HUMAN-BREAST CANCER CELL-LINES AND INHIBITORY EFFECTS OF GNRH ANTAGONISTS [J].

EIDNE, KA ;

FLANAGAN, CA ;

HARRIS, NS ;

MILLAR, RP .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1987, 64 (03) :425-432

[8]

Emons G, 2000, RECENT RES CANCER, V153, P83

[9] THE USE OF LUTEINIZING-HORMONE-RELEASING HORMONE AGONISTS AND ANTAGONISTS IN GYNECOLOGICAL CANCERS [J].

EMONS, G ;

SCHALLY, AV .

HUMAN REPRODUCTION, 1994, 9 (07) :1364-1379

[10] HIGH-AFFINITY BINDING AND DIRECT ANTIPROLIFERATIVE EFFECTS OF LUTEINIZING-HORMONE-RELEASING HORMONE ANALOGS IN HUMAN ENDOMETRIAL CANCER CELL-LINES [J].

EMONS, G ;

SCHRODER, B ;

ORTMANN, O ;

WESTPHALEN, S ;

SCHULZ, KD ;

SCHALLY, AV .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1993, 77 (06) :1458-1464

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