Research article summary (published 30 Oct 2009):

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

Full Abstract

Somatostatin 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. (c) 2009 UICC.

Author information

Author/s: Theodoropoulou, Marily (M); Tichomirowa, Maria A (MA); Sievers, Caroline (C); Yassouridis, Alexander (A); Arzberger, Thomas (T); Hougrand, Olivier (O); Deprez, Manuel (M); Daly, Adrian F (AF); Petrossians, Patrick (P); Pagotto, Uberto (U); Beckers, Albert (A); Stalla, Günter K (GK);

Affiliation: Department of Endocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany. marily(-atsign-)mpipsykl.mpg.de

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 9) : pp 2122-6

Dates: Created 2009/09/03; Completed 2009/09/15;

PMID: 19637311, status: MEDLINE (last retrieval date: 9/15/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acromegaly - drug therapy Adolescent Adult Aged Cell Cycle Proteins - analysis Cohort Studies Female Human Growth Hormone - blood Humans Insulin-Like Growth Factor I - analysis

Insulin-Like Growth Factor I - analysis Male Middle Aged Octreotide - therapeutic use Peptides, Cyclic - therapeutic use Pituitary Neoplasms - chemistry; drug therapy Retrospective Studies Somatostatin - analogs & derivatives; therapeutic use Transcription Factors - analysis Tumor Suppressor Proteins - analysis

Associated Chemicals: Cell Cycle Proteins (0) ; PLAGL1 protein, human (0) ; Peptides, Cyclic (0) ; Transcription Factors (0) ; Tumor Suppressor Proteins (0) ; lanreotide (118992-92-0) ; Human Growth Hormone (12629-01-5) ; Somatostatin (51110-01-1) ; Insulin-Like Growth Factor I (67763-96-6) ; Octreotide (83150-76-9)

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