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PTTG (Securin) as Cancer Biomarker

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Biomarkers in Cancer

Abstract

Pituitary tumor transforming gene (PTTG) has originally been discovered as a gene differentially expressed between rat pituitary tumor cells and normal rat pituitary tissue. It was rapidly recognized that PTTG mRNA and protein are much more abundant in various human tumor types as compared to the corresponding non-tumor tissue. The mammalian PTTG protein was found to be a securin, required for correct sister-chromatid separation and equal distribution of mitotic chromosomes to the daughter cells. Increased levels of the protein in tumor cells result in aneuploidy and DNA instability. The potential of PTTG to initiate and support tumor development was demonstrated in xenograft models. Transgenic mice finally proved a weak oncogenic potential of the gene. PTTG exhibits a vast impact on the transcriptome of tumor cells due to its ability to bind to general transcription factors, such as SP1, and to p53, which is of major importance for cell cycle regulation and apoptosis. Among the PTTG-regulated genes are some which are associated with tumor cell migration and invasion, corresponding to the metastasis-enhancing function of PTTG observed in xenograft models. In several human tumor types, high mRNA and protein levels of PTTG have been associated with increased proliferation index, with increased risk of metastases, and – most important – with lower overall survival. Due to the similarity of results among several clinical studies, including various types of solid tumors, it can be stated that PTTG is a valuable prognostic marker in aggressive human tumor diseases.

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Abbreviations

ACTH:

AdrenoCorticoTropic Hormone

ADH:

AntiDiuretic Hormone

AFP:

Alpha(α)-FetoProtein

bFGF:

basic Fibroblast Growth Factor

ca.:

“circa” (Latin) = approximately (English)

CAB:

Combined Androgen Blockade

ccRCC:

clear cell Renal Cell Carcinoma

cDNA:

complimentary DNA

DNA:

DeoxyriboNucleic Acid

e.g.:

“exempli gratia” (Latin) = for example (English)

ECM:

ExtraCellular Matrix

EGFP:

Enhanced Green Fluorescent Protein

EGFR:

Epidermal Growth Factor Receptor

EMT:

Epithelial to Mesenchymal Transition

ESCC:

Esophageal Squamous Cell Carcinoma

FAK:

Focal Adhesion Kinase

FSH:

Follicle-Stimulating Hormone

g:

Gram

GAPDH:

GlycerAldehyde-3-Phosphate DeHydrogenase

GBM:

GlioBlastoma (Multiforme)

GH:

Growth Hormone

HNSCC:

Head and Neck Squamous Cell Carcinoma

HPF:

High-Power Field

hPTTG:

human PTTG

HR:

High Risk

I:

Iodine

i.e.:

“id est” (Latin) = that is (English)

IDH1:

Isocitrate DeHydrogenase 1

IHC:

ImmunoHistoChemistry

LH:

Luteinizing Hormone

M:

Metastasis

MGMT:

MethylGuanine-DNA MethylTransferase

MI:

Mitotic Index

MMP:

Matrix MetalloProteinase

mRNA:

messenger RNA

MSH:

Melanocyte-Stimulating Hormone

N:

(Lymph)Node

NIS:

Sodium-Iodide Symporter

NSCLC:

Non-Small Cell Lung Carcinoma

p(T,N,M) :

pathological(T,N,M)

PCNA:

Proliferating Cell Nuclear Antigen

PCR:

Polymerase Chain Reaction

PRL:

Prolactin

pTNM:

pathological Tumor-Node-Metastasis

PTTG:

Pituitary Tumor Transforming Gene

p-value :

probability-value

Rb:

Retinoblastoma

RNA:

RiboNucleic Acid

RT-PCR:

Reverse Transcription-PCR

r-value :

correlation coefficient

SCLC:

Small Cell Lung Carcinoma

shRNA:

short hairpin RNA

siRNA:

short interfering RNA

SOP:

Standard Operating Protocols

STAT:

Signal Transducer and Activation of Transcription

STH:

SomatoTropic Hormone

T:

Tumor

TGF:

Tumor Growth Factor

TIMP:

Tissue Inhibitor of MetalloProtease

TSH:

Thyroid-Stimulating Hormone

V:

Vein

VEGF:

Vascular Endothelial Growth Factor

WHO:

World Health Organization

β-Gal:

β-Galactosidase

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Authors and Affiliations

  1. Department of Pathology, Medical Faculty, Democritus University of Thrace, Alexandroupolis, Greece

    Dimitrios N. Kanakis

  2. Department of Neuropathology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany

    Elmar Kirches

Authors
  1. Dimitrios N. Kanakis
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  2. Elmar Kirches
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Corresponding author

Correspondence to Dimitrios N. Kanakis .

Editor information

Editors and Affiliations

  1. Faculty of Life Sciences & Medicine King’s College London, Department of Nutrition and Dietetics Division of Diabetes & Nutritional Scien, London, United Kingdom

    Victor R. Preedy

  2. Faculty of Science & Technology, Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Kanakis, D.N., Kirches, E. (2015). PTTG (Securin) as Cancer Biomarker. In: Preedy, V., Patel, V. (eds) Biomarkers in Cancer. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7681-4_19

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