nach oben

Erschienen in:

01.08.2012 | Research Article

Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact

verfasst von: Maroulio Talieri, Marina Devetzi, Andreas Scorilas, Eleana Pappa, Nikolaos Tsapralis, Ioannis Missitzis, Alexandros Ardavanis

Erschienen in: Tumor Biology | Ausgabe 4/2012

Einloggen, um Zugang zu erhalten

Abstract

Kallikrein-related peptidases (KLKs) are a group of 15 serine proteases, hormonally regulated, and localized on chromosome 19q13.4. Alternative splicing is a process that plays significant role in the development, physiology, and different diseases, like cancer. Kallikrein family numbers more than 82 alternative transcripts. Understanding the role that those gene transcripts play in various cancer types, could lead to the discovery of diagnostic markers or drug targets. The present study was designed to analyze the expression profile of the splice variants of kallikrein-related peptidase 12 (KLK12) in breast cancer patients and to evaluate their clinical significance. KLK12 splice variants (KLK12sv3 and KLK12sv1/KLK12sv2) were examined in 69 tissue samples of breast cancer using quantitative real-time PCR as well as semi-quantitative PCR. Relative quantitative expression of KLK12 was statistically associated to clinicopathological parameters. From the splice variants examined, statistical associations with clinicopathological parameters were obtained only from KLK12sv3 variant. KLK12sv3 is more frequently expressed in tumors of lower grade (p = 0.040), early patient TNM stage (p = 0.024), and smaller tumor size (p = 0.023). Positive KLK12sv3 expression is associated with longer patient disease-free survival (DFS) (p = 0.042) and higher progesterone receptor concentration (p = 0.008). KLK12sv1/KLK12sv2 expression is statistically associated with KLK12sv3 expression (p = 0.001). KLK12sv3 can be regarded as a marker of good prognosis in breast cancer.

Smith RA, Cokkinides V, Brooks D, Saslow D, Shah M, Brawley OW. Cancer Screening in the United States, 2010: A Review of Current American. Cancer Society Guidelines and Issues in Cancer Screening. CA Cancer J Clin. 2010;60:99–119.PubMed

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMed

Lopez-Otin C, Lynn MM. Emerging roles of proteases in tumor suppression. Nat Rev Cancer. 2007;7:800–8.PubMed

Lawrence MG, Lai J, Clements JA. Kallikreins on steroids: structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus. Endocrine Rev. 2010;31:407–46.

Eissa A, Diamandis EP. Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions. Biol Chem. 2008;389:669–80.PubMed

Borgono CA, Diamandis EP. The emerging roles of human kallikreins in cancer. Nat Rev Cancer. 2004;4:876–90.PubMed

Pampalakis G, Sotiropoulou G. Tissue kallikrein proteolytic cascade pathways in normal physiology and cancer. Biochim Biophys Acta. 2007;1776:22–31.PubMed

Lu Y, Papagerakis P, Yamakoshi Y, Hu JCC, Bartlett JD, Simmer JP. Functions of KLK4 and MMP-20 in dental enamel formation. Biol Chem. 2008;389:695–700.PubMedPubMedCentral

Scarisbrick IA, Limbo R, Vandell AG, Keegan M, Blaber SI, Blaber M, et al. Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration. Biol Chem. 2008;389:739–46.PubMedPubMedCentral

10.

Oikonomopoulou K, Hansen KK, Chapman K, Vergnolle N, Diamandis EP, Hollenberg MD. Kallikrein-mediated activation of PARs in inflammation and nociception. Inflamm Res 2007;56, Suppl 3:s499–s502.

11.

Shaw JLV, Diamandis EP. A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology. Biol Chem. 2008;389:681–8.PubMed

12.

Smith Jr RS, Gao L, Chao L, Chao J. Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia. Biol Chem. 2008;389:725–30.PubMed

13.

Sotiropoulou G, Pampalakis G, Diamandis EP. Functional roles of human kallikrein-related peptidases. J Biol Chem. 2009;284:32989–94.PubMedPubMedCentral

14.

Sotiropoulou G, Pampalakis G. Kallikrein-related peptidases: bridges between immune functions and extracellular matrix degradation. Biol Chem. 2010;391:321–31.PubMed

15.

Υoon H, Blaber S, Evans DM, Trim J, Juliano MA, Scaristrick IA, et al. Activation profiles of human kallikrein-related peptidases by proteinases of thrombostasis axis. Protein Sci. 2008;11:1998–2007.

16.

Blaber M, Yoon H, Juliano MA, Scarisbrick IA, Blaber SI. Functional intersection of the kallirein-related peptidases (KLKs) and thrombostasis axis. Biol Chem. 2010;391:311–20.PubMedPubMedCentral

17.

Oikonomopoulou K, Diamandis EP, Hollenberg MD. Kallikrein-related peptidases: proteolysis and signaling in cancer, the new frontier. Biol Chem. 2010;391:299–310.PubMed

18.

Michael IP, Kurlender L, Memari N, Yousef GM, Du D, Grass L, et al. Intron retention: a common splicing event within the human kallikrein gene family. Clin Chem. 2005;51:506–15.PubMed

19.

Kurlender L, Borgono C, Michael I, Obiezu Ch, Elliott MB, Yousef GM, et al. A survey of alternative transcripts of human tissue kallikrein genes. Biochim Biophys Acta. 2005;1755:1–14.PubMed

20.

Tan OL, Whitbread AK, Clements JA, Dong Y. Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function? Biol Chem. 2006;387:697–705.PubMed

21.

Yousef GM, Magklara A, Diamandis EP. KLK12 is a novel serine protease and a new member of the human kallikrein gene family: differential expression in breast cancer. Genomics. 2000;69:331–41.PubMed

22.

Lundwall A, Band V, Blaber M, Clements J, Courty Y, Diamandis E, et al. A comprehensive nomenclature for serine proteases with homology to the tissue kallikrein. Biol Chem. 2006;387:637–41.PubMed

23.

Komatsu N, Takata M, Otsuki N, Toyama T, Ohka R, Takehara K, et al. Expression and localization of tissue kallikrein mRNAs in human epidermis and appendages. J Invest Dermatol. 2003;121:542–9.PubMed

24.

Memari N, Weiping J, Diamandis EP, Luo LY. Enzymatic properties of human kallikrein-related peptidase 12 (KLK12). Biol Chem. 2007;388:427–35.PubMed

25.

Yoon H, Laxmikanthan G, Lee J, Blaber SI, Rodriquez A, Kogot JM, et al. Activation profiles and regulatory cascades of the human kallikrein-related peptidases. J Biol Chem. 2007;282:31852–64.PubMed

26.

Giusti B, Serrati S, Margheri F, Papucci L, Rossi L, Poggi F, et al. The antiangiogenic tissue kallikrein pattern of endothelial cells in systemic sclerosis. Arthritis Rheum. 2005;52:3618–28.PubMed

27.

Scorilas A, Talieri M, Ardavanis A, Courtis N, Dimitriadis E, Yotis J, et al. Polyadenylate polymerase enzymatic activity in mammary tumor cytosols: a new independent prognostic marker in primary breast cancer. Cancer Res. 2000;60:5427–33.PubMed

28.

Talieri M, Mathioudaki K, Prezas P, Alexopoulou DK, Diamandis EP, Xynopoulos D, et al. Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer. Thromb Haemost. 2009;101:741–7.PubMed

29.

Talieri M, Alexopoulou DK, Scorilas A, Kypraios D, Arnogiannaki N, Devetzi M, et al. Expression analysis and clinical evaluation of kallikrein-related peptidase 10 (KLK10) in colorectal cancer. Tumor Biol. 2011;32:737–44.

30.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (−Delta Delta C(T)) method. Methods. 2001;5:402–8.

31.

Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10:7252–9.PubMed

32.

Black DL. Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology. Cell. 2000;103:367–70.PubMed

33.

Thorsen K, Sorensen KD, Brems-Eskilden AS, Modin Ch, Gaustadnes M, Hein A-MK, et al. Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis. Mol Cel Proteomics. 2008;7:1214–24.

34.

Blair ChA, Xiaolin Z. Potential molecular targeting of splice variants for cancer treatment. Indian J Exp Biol. 2011;49:836–9.PubMedPubMedCentral

35.

Dong Y, Kaushal A, Brattsand M, Nicklin J, Clements JA. Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers. Clin Cancer Res. 2003;1719:1710–20.

36.

Dong Y, Bui LT, Odorico DM, Tan OL, Myers SA, Samaratunga H, et al. Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms. Endocrine-Relat Cancer. 2005;12:875–89.

37.

Planque Ch, Choi Y-H, Guyetant S, Heuze-Vourc’h N, Briollais L, Courty Y. Alternative splicing variant of kallikrein-related peptidase 8 as an independent predictor of unfavorable prognosis in lung cancer. Clin Chem. 2010;56:987–97.PubMed

38.

Heuze-Vourc’h N, Leblond V, Courty Y. Complex alternative splicing of the hKLK3 gene coding for the tumor marker PSA (prostate-specific-antigen). Eur J Biochem. 2003;270:706–14.PubMed

39.

Memari N, Diamandis EP, Earle T, Campbell A, Van Dekken H, Van der Kwast TH. Human kallikrein-related peptidase 12 antibody generation and immunohistochemical localization in prostatic tissues. Prostate. 2007;67:1465–74.PubMed

40.

Mitsui S, Yamada T, Okui A, Kominami K, Uemura H, Yamaguchi N. A novel isoform of a kallikrein-like protease, TLSP/hippostasin, (PRSS20), is expressed in the human brain and prostate. Biochem Biophys Res Commun. 2000;272:205–11.PubMed

41.

Mauridis K, Avgeris M, Koutalellis G, Stravodimos K, Scorilas A. Expression analysis and study of the KLK15 mRNA splice variants in prostate cancer and benign prostatic hyperplasia. Cancer Scie. 2010;101:693–9.

42.

Slawin KM, Shariat Sh, Nguyen C, Leventis AK, Song W, Kattan MW, et al. Detection of metastatic prostate cancer using a splice variant-specific reverse transcriptase-polymerase chain reaction assay for grandular kallikrein. Cancer Res. 2000;60:7142–8.PubMed

43.

David A, Mabjeesh N, Azar I, Biton Sh, Engel Sh, Bernstein J, et al. Unusual alternative splicing within the human kallikrein genes KLK2 and KLK3 give rise to novel prostate-specific proteins. J Biol Chem. 2002;277:18084–90.PubMed

44.

Nakamura T, Mitsui Sh, Okui A, Miki T, Yamagushi N. Molecular cloning and expression of a variant form of hippostasin/KLK11 in prostate. Prostate. 2003;54:299–305.PubMed

45.

Shaw JL, Diamandis EP. Distribution of 15 human kallikreins in tissues and biological fluids. Clin Chem. 2007;53:1423–32.PubMed

46.

Kim JT, Song EY, Chung K-S, Kang MA, Kim JW, Kim SJ, et al. Up-regulation and clinical significance of serine protease kallikrein 6 in colon cancer. Cancer. 2011;177:2608–19.

47.

Harvey TJ, Hooper JD, Myers SA, Stephenson SA, Ashworth LK, Clements JA. Tissue-specific expression patterns and fine mapping of the human kallikrein (KLK) locus on proximal 19q13.4. J Biol Chem. 2000;275:37397–406.PubMed

48.

Goyal J, Smith KM, Cowan JM, Wazer DE, Lee SW, Band V. The role for NES1 serine protease as a novel tumor suppressor. Cancer Res. 1998;58:4782–6.PubMed

49.

Borgono CA, Michael IP, Komatsu N, Jayakumar A, Kapadia R, Clayman GL, et al. A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. J Biol Chem. 2007;282:3640–52.PubMed

50.

Shaw JLV, Petraki C, Watson C, Bocking A, Diamandis EP. Role of tissue kallikrein-related peptidases in cervical mucus remodeling and host defense. Biol Chem. 2008;389:1513–22.PubMed

Titel: Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact
verfasst von: Maroulio Talieri
Marina Devetzi
Andreas Scorilas
Eleana Pappa
Nikolaos Tsapralis
Ioannis Missitzis
Alexandros Ardavanis
Publikationsdatum: 01.08.2012
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 4/2012
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-012-0347-x

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact

Abstract

Neu im Fachgebiet Onkologie

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Update Onkologie

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2012

Serum HE4 as a diagnostic and prognostic marker for lung cancer

Serum C-reactive protein as an important prognostic variable in patients with diffuse large B cell lymphoma

Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines

Prognostic significance of transforming growth factor beta (TGF-β) signaling axis molecules and E-cadherin in colorectal cancer

The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer

Impact of codon 72 Arg > Pro single nucleotide polymorphism in TP53 gene in the risk of kangri cancer: a case control study in Kashmir

Neu im Fachgebiet Onkologie

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Update Onkologie