Klocker Helmut, ao.Univ.-Prof. Mag.Dr.rer.nat.

University / Clinic: Innsbruck Medical University
Institute: Department of Urology, Urological Laboratory and Division of Experimental Urology
 
Research Area: Molecular Oncology

Email: helmut.klocker@uki.at
Web: http://urolab.uki.at/page.cfm?vpath=index


Research Topic:
In the focus of research are the molecular mechanisms that underlay prostate cancer carcinogenesis, tumor progression and development of therapy resistance. A key molecule in prostate cancer is the androgen receptor, the target of the different kind of hormone ablation therapies used for cancer therapy. Androgens, acting through the androgen receptor, stimulate growth and survival of tumor cells. In the therapy-resistant stage the androgen receptor is hyperreactive and annihilates therapeutic intervention through mutations, gene amplification, overexpression and cross-talk with growth factor signal cascades such as the insulin-like growth factor axis. купить одеяло киев


The aim of the projects is the characterization and better understanding of the function of the androgen receptor and interacting regulatory networks,their alterations in tumor progression and therapy resistance and new modes of targeting them. Using different OMICS profiling techniques crucial regulatory network changes and their target genes are identified and subsequently functionally analyzed. We expect that this will result in a better insight into the function of the hyperreactive androgen receptor and dysregulated IGF axis and allow identification of new potential targets for therapy of advanced prostate tumors. одеяло


Project:
  Identification and characterization of androgen-regulated genes involved in prostate carcinogenesis and prostate cancer progression.
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Selected publications:
 
  Pichler R, Fritz J, Heidegger I, Steiner E, Culig Z, Klocker H, Fuchs D
The predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer.
Cancer Sci. 2017 Jan 20. doi: 10.1111/cas.13171. [Epub ahead of print]

  Höfer J, Akbor M, Handle F, Ofer P, Puhr M, Parson W, Culig Z, Klocker H, Heidegger I
Critical role of androgen receptor level in prostate cancer cell resistance to new generation antiandrogen enzalutamide.
Oncotarget. 2016 Sep 13;7(37):59781-59794. doi: 10.18632/oncotarget.10926.

  Pasqualini L, Bu H, Puhr M, Narisu N, Rainer J, Schlick B, Schäfer G, Angelova M, Trajanoski Z, Börno S, Schweiger M, Fuchsberger C, Klocker H
miR-22 and miR-29a Are Members of the Androgen Receptor Cistrome Modulating LAMC1 and Mcl-1 in Prostate Cancer.
Mol Endocrinol. 2015 Jul;29(7):1037-54.

  Santer F, Erb H, Oh S, Handle F, Feiersinger G, Luef B, Bu H, Schäfer G, Ploner C, Egger M, Rane J, Maitland N, Klocker H, Eder I, Culig Z
Mechanistic rationale for Mcl1 inhibition during androgen deprivation therapy
Oncotarget. 2015 Mar 20;6(8):6105-22.

  Heidegger I, Höfer J, Luger M, Pichler R, Klocker H, Horninger W, Steiner E, Jochberger S, Culig Z
Is Eotaxin-1 a serum and urinary biomarker for prostate cancer detection and recurrence?
Prostate. 2015 Dec;75(16):1904-9. doi: 10.1002/pros.23086. Epub 2015 Aug 26.

  Pichler R, Borena W, Schäfer G, Manzl C, Culig Z, List S, Neururer S, Von Laer D, Heidegger I, Klocker H, Horninger W, Steiner H, Brunner A
Low prevalence of HPV detection and genotyping in non-muscle invasive bladder cancer using single-step PCR followed by reverse line blot.
World J Urol. 2015 Dec;33(12):2145-51. doi: 10.1007/s00345-015-1539-y. Epub 2015 Mar 19.

  Ofer P, Heidegger I, Eder I, Schöpf B, Neuwirt H, Geley S, Klocker H, Massoner P
Both IGF1R and INSR Knockdown Exert Antitumorigenic Effects in Prostate Cancer In Vitro and In Vivo.
Mol Endocrinol. 2015 Dec;29(12):1694-707. doi: 10.1210/me.2015-1073. Epub 2015 Oct 9.

  Höfer J, Kern J, Ofer P, Eder I, Schäfer G, Dietrich D, Kristiansen G, Geley S, Rainer J, Gunsilius E, Klocker H, Culig Z, Puhr M
SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer.
Endocr Relat Cancer. 2014 Jan 30;

  Massoner P, Thomm T, Mack B, Untergasser G, Martowicz A, Bobowski K, Klocker H, Gires O, Puhr M
EpCAM is overexpressed in local and metastatic prostate cancer, suppressed by chemotherapy and modulated by MET-associated miRNA-200c/205.
Br J Cancer. 2014 Aug 26;111(5):955-64.

  Heidegger I, Kern J, Ofer P, Klocker H, Massoner P
Oncogenic functions of IGF1R and INSR in prostate cancer include enhanced tumor growth, cell migration and angiogenesis.
Oncotarget. 2014 May 15;5(9):2723-35.

  Heidegger I, Klocker H, Steiner E, Skradski V, Ladurner M, Pichler R, Schäfer G, Horninger W, Bektic J
[-2]proPSA is an early marker for prostate cancer aggressiveness.
Prostate Cancer Prostatic Dis. 2014 Mar;17(1):70-4.

  Köhler A, Demir Ü, Kickstein E, Krauss S, Aigner J, Aranda-Orgillés B, Karagiannidis A, Achmüller C, Bu H, Wunderlich A, Schweiger M, Schäfer G, Schweiger S, Klocker H, Schneider R
A hormone-dependent feedback-loop controls androgen receptor levels by limiting MID1, a novel translation enhancer and promoter of oncogenic signaling.
Mol Cancer. 2014 Jun 9;13:146.

  Demir Ü, Köhler A, Schneider R, Schweiger S, Klocker H
Metformin anti-tumor effect via disruption of the MID1 translational regulator complex and AR downregulation in prostate cancer cells.
BMC Cancer. 2014 Jan 31;14:52.

  Puhr M, Höfer J, Neuwirt H, Eder I, Kern J, Schäfer G, Geley S, Heidegger I, Klocker H, Culig Z
PIAS1 is a crucial factor for prostate cancer cell survival and a valid target in docetaxel resistant cells.
Oncotarget. 2014 Dec 15;5(23):12043-56.

  Heidegger I, Massoner P, Eder I, Pircher A, Pichler R, Aigner F, Bektic J, Horninger W, Klocker H
Novel therapeutic approaches for the treatment of castration-resistant prostate cancer.
J Steroid Biochem Mol Biol. 2013 Jun 20;138C:248-256.

  Bu H, Schweiger M, Manke T, Wunderlich A, Timmermann B, Kerick M, Pasqualini L, Shehu E, Fuchsberger C, Cato A, Klocker H
Anterior gradient 2 and 3--two prototype androgen-responsive genes transcriptionally upregulated by androgens and by oestrogens in prostate cancer cells
FEBS J. 2013 Mar;280(5):1249-66.

  Heidegger I, Pichler R, Müller B, Klocker H, Oswald D, Haid B, Zelger B, Horninger W, Oswald J
Is real-time PCR the correct method to evaluate the incidence of human papillomavirus in prepuces of asymptomatic boys and men?
World J Urol. 2013 Oct 22.

  Höfer J, Schäfer G, Klocker H, Erb H, Mills I, Hengst L, Puhr M, Culig Z
PIAS1 is increased in human prostate cancer and enhances proliferation through inhibition of p21.
Am J Pathol. 2012 May;180(5):2097-107. Epub 2012 Mar 23.

  Puhr M, Höfer J, Schäfer G, Erb H, Oh S, Klocker H, Heidegger I, Neuwirt H, Culig Z
Epithelial to Mesenchymal Transition Leads to Docetaxel Resistance in Prostate Cancer and is Mediated by Reduced Expression of miR-200c and miR-205.
Am J Pathol. 2012 Oct 3. pii: S0002-9440(12)00653-0. doi: 10.1016/j.ajpath.2012.08.011

  Heidegger I, Ofer P, Doppler W, Rotter V, Klocker H, Massoner P
Diverse functions of IGF/insulin signaling in malignant and non-cancerous prostate cells: proliferation in cancer cells and differentiation in non-cancerous cells.
Endocrinology. 2012 Oct;153(10):4633-43

  Kong L, Schäfer G, Bu H, Zhang Y, Zhang Y, Klocker H
Lamin A/C protein is overexpressed in tissue-invading prostate cancer and promotes prostate cancer cell growth, migration and invasion through the PI3K/AKT/PTEN pathway.
Carcinogenesis. 33:751-9, 2012.

  Heidegger I, Ladurner M, Skradski V, Klocker H, Schäfer G, Horninger W, Bektic J
Adverse pathological findings in needle biopsy gleason score 6 prostate cancers with low and intermediate preoperative PSA levels following radical prostatectomy.
Anticancer Res. 2012 Dec;32(12):5481-5.

  Bu H, Bormann S, Schäfer G, Horninger W, Massoner P, Neeb A, Lakshmanan V, Maddalo D, Nestl A, Sültmann H, Cato A, Klocker H
The anterior gradient 2 (AGR2) gene is overexpresses in prostate cancer and is a urine sediment marker for prostate cancer detection.
Prostate. 2011 May;71(6):575-87. doi: 10.1002/pros.21273. Epub 2010 Oct 13

  Kerick M, Isau M, Timmermann B, Sultmann H, Herwig R, Krobitsch S, Schäfer G, Verdorfer I, Bartsch G, Klocker H, Lehrach H, Schweiger M
Targeted high throughput sequencing in clinical cancer settings: formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity.
BMC Med Genomics. 4:68, 2011.

  Heidegger I, Pircher A, Klocker H, Massoner P
Targeting the insulin-like growth factor network in cancer therapy.
Cancer Biol Ther. 2011 Apr 15;11(8):701-7

  Massoner P, Ladurner Rennau M, Heidegger I, Kloss-Brandstätter A, Summerer M, Reichhart E, Schäfer G, Klocker H
Expression of the IGF axis is decreased in local prostate cancer but enhanced after benign prostate epithelial differentiation and TGF-beta treatment.
Am J Pathol. 179:2905-19, 2011.

  Skvortsov S, Schäfer G, Stasyk T, Fuchsberger C, Bonn G, Bartsch G, Klocker H, Huber L
Proteomics profiling of microdissected low- and high-grade prostate tumors identifies Lamin A as a discriminatory biomarker.
J Proteome Res. 10:259-68, 2011.

  Desiniotis A, Schäfer G, Klocker H, Eder I
Enhanced antiproliferative and proapoptotic effects on prostate cancer cells by simultaneously inhibiting androgen receptor and cAMP-dependent protein kinase A.
Int J Cancer. 126:775-89, 2010.

  Kloss-Brandstätter A, Schäfer G, Erhart G, Hüttenhofer A, Coassin S, Seifarth C, Summerer M, Bektic J, Klocker H, Kronenberg F
Somatic mutations throughout the entire mitochondrial genome are associated with elevated PSA levels in prostate cancer patients.
Am J Hum Genet. 87:802-12, 2010.

  Setlur S, Chen C, Hossain R, Ha J, Van Doren V, Stenzel B, Steiner E, Oldridge D, Kitabayashi N, Banerjee S, Chen J, Schäfer G, Horninger W, Lee C, Rubin M, Klocker H, Demichelis F
Genetic variation of genes involved in dihydrotestosterone metabolism and the risk of prostate cancer.
Cancer Epidemiol Biomarkers Prev. 19:229-39, 2010.

  Massoner P, Colleselli D, Matscheski A, Pircher H, Geley S, Jansen-Dürr P, Klocker H
Novel mechanism of IGF-binding protein-3 action on prostate cancer cells: inhibition of proliferation, adhesion, and motility
Endocr Relat Cancer. 16:795-808

  Massoner P, Haag P, Seifarth C, Jurgeit A, Rogatsch H, Doppler W, Bartsch G, Klocker H
Insulin-like growth factor binding protein-3 (IGFBP-3) in the prostate and in prostate cancer: local production, distribution and secretion pattern indicate a role in stromal-epithelial interaction
Prostate. 2008 Aug 1;68(11):1165-78

  Bartsch G, Horninger W, Klocker H, Pelzer A, Bektic J, Oberaigner W, Schennach H, Schäfer G, Frauscher F, Boniol M, Severi G, Robertson C, Boyle P; Tyrol Prostate Cancer Screening Group
Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality
BJU Int. 2008 Apr;101(7):809-16

  Jurgeit A, Berlato C, Obrist P, Ploner C, Massoner P, Schmölzer J, Haffner M, Klocker H, Huber L, Geley S, Doppler W
Insulin-Like Growth Factor Binding Protein (Igfbp)-5 Enters Vesicular Structures but Not the Nucleus.
Traffic 8(12):1815-1828

  Comuzzi B, Lambrinidis L, Rogatsch H, Godoy-Tundidor S, Knezevic N, Krhen I, Marekovic Z, Bartsch G, Klocker H, Hobisch A, Culig Z
The transcriptional co-activator cAMP response element-binding protein-binding protein is expressed in prostate cancer and enhances androgen- and anti-androgen-induced androgen receptor function
Am J Pathol 162:233-241, 2003.