Tumor ZAC1 expression is associated with the response to somatostatin analog therapy in patients with acromegaly

International Journal of Cancer - Tập 125 Số 9 - Trang 2122-2126 - 2009
Marily Theodoropoulou1,2, María A. Tichomirowa3,2, Caroline Sievers1,2, Alexander Yassouridis4, Thomas Arzberger5, Olivier Hougrand6, Manuel Deprez6, Adrian Daly3, Patrick Pétrossians3, Uberto Pagotto7, Albert Beckers3, Günter K. Stalla1
1Department of Endocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany
2The first three authors contributed equally to this work.
3Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, 4000 Liège, Belgium
4Research Group of Statistics, Max Planck Institute of Psychiatry, 80804 Munich, Germany
5Center for Neuropathology and Prion Research, München Ludwig-Maximilians-University, Munich, Germany
6Department of Pathology, Centre Hospitalier Universitaire de Liège, University of Liège, 4000 Liège, Belgium
7Endocrine Unit, Department of Internal Medicine and Gastroenterology, Center for Applied Biomedical Research, S. Orsola-Malpighi General Hospital, 40138 Bologna, Italy

Tóm tắt

AbstractSomatostatin analogs (SSA) with their potent antisecretory and antiproliferative effects are the main medical treatment option for patients with neuroendocrine tumors, such as gastroenteropancreatic and acromegaly‐associated growth hormone secreting pituitary tumors. Although a good portion of acromegalic patients gets normalized after SSA treatment, strict hormonal control is not achieved in a sizeable proportion of these patients. The reasons for this incomplete response to SSA treatment are unclear. We have found that the tumor suppressor ZAC1 (LOT1/PLAGL1) is essential for the antiproliferative effect of SSA in pituitary tumor cells. The aim of the present retrospective cohort study was to determine whether ZAC1 immunoreactivity in archival somatotrophinoma tissue derived from 45 patients with acromegaly routinely pretreated with SSA before surgery, was associated with response to SSA (normalization of GH, IGF‐I and presence of tumor shrinkage). All tumors displayed ZAC1 immunoreactivity [weak (+; n = 15), moderate (++; n = 16) and strong (+++; n = 14)]. A significant positive correlation was found between strong ZAC1 immunoreactivity and IGF‐I normalization and presence of tumor shrinkage after SSA treatment, which was not affected by age at diagnosis, gender or duration of SSA treatment. These in vivo data combined with the antiproliferative properties of ZAC1/Zac1 provide evidence of a mechanistic role for this transcription factor on SSA induced tumor shrinkage and hormone normalization. © 2009 UICC

Từ khóa


Tài liệu tham khảo

10.1038/nrd1255

10.1056/NEJMra062453

10.1210/jc.2007-1191

10.1210/jc.2006-1668

10.1111/j.1365-2265.2008.03221.x

10.1210/jc.2005-0260

10.1210/jc.2005-2347

10.1016/S0026-0495(96)90088-8

10.1210/jc.2008-1351

10.1210/jc.2004-1093

10.1210/jc.2004-2466

10.1530/eje.1.01968

10.1016/0024-3205(95)02082-T

10.1210/endo.136.10.7664634

10.1006/bbrc.1995.1517

10.1002/(SICI)1097-0215(19980413)76:2<259::AID-IJC14>3.0.CO;2-7

10.1158/0008-5472.CAN-05-1189

Pagotto U, 2000, The expression of the antiproliferative gene ZAC is lost or highly reduced in nonfunctioning pituitary adenomas, Cancer Res, 60, 6794

10.1093/emboj/16.10.2814

10.1016/j.devcel.2006.09.003

10.1210/endo.140.2.6532

10.1210/jc.2005-1208

10.1210/jc.2005-0998

10.1210/jcem.86.11.7986

10.1210/me.10.12.1688

10.1677/erc.1.01191

10.1210/jc.79.1.113

10.1530/eje.1.01824

10.1002/ijc.22816

10.1210/jcem-68-4-844

10.1159/000182500

10.1046/j.1365-2265.1997.3361119.x

10.1210/jc.84.8.2759

10.1210/jc.85.2.781

10.1007/s12022-007-9004-0

10.1158/0008-5472.CAN-08-1857

10.1210/jcem.86.8.7787

10.1158/0008-5472.CAN-06-1529

Thông tin
Thông tin xuất bản

International Journal of Cancer

Tập 125 Số 9

2122-2126

Thông tin tác giả