nach oben

Archives of Gynecology and Obstetrics

Erschienen in:

01.05.2011 | Gynecologic Oncology

Expression and methylation status of the Syk gene in cervical carcinoma

verfasst von: Shuping Zhao, Guixia Sun, Parks W. Tony, Dehua Ma, Chengquan Zhao

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 5/2011

Einloggen, um Zugang zu erhalten

Abstract

Objective

Spleen tyrosine kinase (Syk), a non-receptor protein tyrosine kinase, has recently been recognized as a new candidate tumor suppressor. Decrease or loss of Syk expression has been associated with a malignant phenotype and poor prognosis in a variety of cancers. This study aimed to determine the precise role of Syk in cervical cancer.

Methods

Methylation-specific PCR (MSP) and RT-PCR were utilized to analyze the methylation status and Syk mRNA expression in tissue samples from 20 normal controls, 50 CIN patients and 60 cervical cancer patients.

Results

Syk expression was detected in all 20 normal cervical tissues, as well as in all 18 CIN1 samples. Syk expression was found in 18 of 32 (56%) of CIN2/3 samples.

Conclusion

The results indicate a potential link between the loss of Syk expression and cervical carcinogenesis.

Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156PubMedCrossRef

zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350PubMedCrossRef

Magnusson PK, Gyllensten UB (2000) Cervical cancer risk: is there a genetic component? Mol Med Today 6:145–148PubMedCrossRef

Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Cancer 3:415–428

Baylin SB, Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16:168–174PubMedCrossRef

Jones PA, Laird PW (1999) Cancer epigenetics comes of age. Nat Genet 21:163–167PubMedCrossRef

Katargin AN, Pavlova LS, Kisseljov FL, Kisseljova NP (2009) Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer. BMC Med Genomics 2:30

Ki KD, Lee SK, Tong SY, Lee JM, Song DH, Chi SG (2008) Role of 5′-CpG island hypermethylation of the FHIT gene in cervical carcinoma. J Gynecol Oncol 19(2):117–122PubMedCrossRef

Ongenaert M, Wisman GB, Volders HH, Koning AJ, Zee AG, van Criekinge W, Schuuring E (2008) Discovery of DNA methylation markers in cervical cancer using relaxation ranking. BMC Med Genomics 1:57

10.

Zhao XL, Meng ZY, Qiao YH, Zhang HL (2008) Promoter methylation of DAPK gene in cervical carcinoma. Ai Zheng 27(9):919–923 (Chinese Journal)PubMed

11.

Gokul G, Gautami B, Malathi S, Sowjanya AP, Poli UR, Jain M, Ramakrishna G, Khosla S (2007) DNA methylation profile at the DNMT3L promoter: a potential biomarker for cervical cancer. Epigenetics 2(2):80–85PubMedCrossRef

12.

Shivapurkar N, Sherman ME, Stastny V, Echebiri C, Rader JS, Nayar R, Bonfiglio TA, Gazdar AF, Wang SS (2007) Evaluation of candidate methylation markers to detect cervical neoplasia. Gynecol Oncol 107(3):549–553PubMedCrossRef

13.

Oikonomou P, Messinis I, Tsezou A (2007) DNA methylation is not likely to be responsible for hTERT expression in premalignant cervical lesions. Exp Biol Med (Maywood) 232(7):881–886

14.

Feng Q, Hawes SE, Stern JE, Dem A, Sow PS, Dembele B, Toure P, Sova P, Laird PW, Kiviat NB (2007) Promoter hypermethylation of tumor suppressor genes in urine from patients with cervical neoplasia. Cancer Epidemiol Biomarkers Prev 16(6):1178–1184PubMedCrossRef

15.

Kitkumthorn N, Yanatatsanajit P, Kiatpongsan S, Phokaew C, Triratanachat S, Trivijitsilp P, Termrungruanglert W, Tresukosol D, Niruthisard S, Mutirangura A (2006) Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer. BMC Cancer 6:55

16.

Coopman PJ, Do MT, Barth M et al (2000) The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells. Nature 406(8):742–747PubMedCrossRef

17.

Ulanova M, Puttagunta L, Marcet-Palacios M, Duszyk M, Steinhoff U, Duta F, Kim MK, Indik ZK, Schreiber AD, Befus AD (2005) Syk tyrosine kinase participates in betal-integrin signaling and inflammatory responses in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 288(3):497–507CrossRef

18.

Yamada T, Fujieda S, Yanagi S, Yamamura H, Inatome R, Sunaga H, Saito H (2001) Protein-tyrosine kinase Syk expressed in human nasal fibroblasts and its effect on RANTES production. J Immunol 166(1):538–543PubMed

19.

Inatome R, Yanagi S, Takano T, Yamamura H (2001) A critical role for Syk in endothelial cell proliferation and migration. Biochem Biophys Res Commun 286(1):195–199PubMedCrossRef

20.

Tsujimura T, Yanagi S, Inatome R, Takano T, Ishihara I, Mitsui N, Takahashi S, Yamamura H (2001) Syk protein-tyrosine kinase is involved in neuron-like differentiation of embryonal carcinoma P19 cells. FEBS Lett 489(2–3):129–133PubMedCrossRef

21.

Yuan Y, Wang J, Li J, Wang L, Li M, Yang Z, Zhang C, Dai JL (2006) Frequent epigenetic inactivation of spleen tyrosine kinase gene in human hepatocellular carcinoma. Clin Cancer Res 12(22):6687–6695

22.

Hoeller C, Thallinger C, Pratscher B, Bister MD, Schicher N, Loewe R, Heere-Ress E, Roka F, Sexl V, Pehamberger H (2005) The non-receptor-associated tyrosine kinase Syk is a regulator of metastatic behavior in human melanoma cells. J Invest Dermatol 124(6):1293–1299PubMedCrossRef

23.

Turner M, Schweighoffer E, Colucci F, Di Santo JP, Tybulewicz VL (2000) Tyrosine kinase SYK: essential functions for immunoreceptor signaling. Immunol Today 21(3):148–154PubMedCrossRef

24.

Kurosaki T (1997) Molecular mechanisms in B cell antigen receptor signaling. Curr Opin Immunol 9:309–318PubMedCrossRef

25.

Chu DH, Morita CT, Weiss A (1998) The Syk family of protein tyrosine kinases in T-cell activation and development. Immunol Rev 165:167–180PubMedCrossRef

26.

Kiefer F, Brumell J, Al-Alawi N, Latour S, Cheng A, Veillette A, Grinstein S, Pawson T (1998) The Syk protein tyrosine kinase is essential for Fcγ receptor signaling in macrophages and neutrophils. Mol Cell Biol 18:4209–4220PubMed

27.

Rumbaugh KM, Binstadt BA, Billadeau DD, Schoon RA, Dick CJ, Ten RM, Leibson PJ (1997) Functional role for Syk tyrosine kinase in natural killer cell-mediated natural cytotoxicity. J Exp Med 186:1965–1974CrossRef

28.

Yanagi S, Inatome R, Takano T, Yamamura H (2001) Syk expression and novel function in a wide variety of tissues. Biochem Biophys Res Commun 288:495–498PubMedCrossRef

29.

Sada K, Takano T, Yanagi S, Yamamura H (2001) Structure and function of Syk protein-tyrosine kinase. J Biochem 130:177–186PubMed

30.

Yuan Y, Mendez R, Sahin A, Dai JL (2001) Hypermethylation leads to silencing of the SYK gene in human breast cancer. Cancer Res 61:5558–5561PubMed

31.

Toyama T, Iwase H, Yamashita H, Hara Y, Omoto Y, Sugiura H, Zhang Z, Fujii Y (2003) Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer. Cancer Lett 189(1):97–102PubMedCrossRef

32.

Ding YB, Wu ZY, Wang S, Zha XM, Zheng W, Liu XA, Fan P (2004) Hypermethylation of Syk gene in promoter region is associated with oncogenesis, metastasis of breast carcinoma. Natl Med J China 84:290–293

33.

Zhang X, Shrikhande U, Alicie BM, Zhou Q, Geahlen RL (2009) A role for the protein-tyrosine kinase, Syk, in regulating cell-cell adhesion and motility in breast cancer cells. Mol Cancer Res 7(5):634–644

34.

Lu J, Lin WH, Chen SY, Longnecker R, Tsai SC, Chen CL, Tsai CH (2006) Syk tyrosine kinases mediates Epstein–Barr virus latent membrane protein 2A-induced cell migration in epithelial cells. J Biol Chem 281:8806–8814PubMedCrossRef

35.

Luangdilok S, Box C, Patterson L, Court W, Harrington K, Pitkin L, Rhŷs-Evans P, O-charoenrat P, Eccles S (2007) Syk tyrosine kinases is linked to cell motility and progression in squamous cell carcinomas of the head and neck. Cancer Res 67:7907–7916PubMedCrossRef

36.

Nakashima H, Natsugoe S, Ishigami S, Okumura H, Matsumoto M, Hokita S, Aikou T (2006) Clinical significance of nuclear expression of spleen tyrosine kinase (Syk) in gastric cancer. Cancer Lett 236(1):89–94PubMedCrossRef

37.

Li J, Sidell N (2005) Growth-related oncogene produced in human breast cancer cells and regulated by Syk protein-tyrosine kinase. Int J Cancer 117:14–20PubMedCrossRef

38.

Yang ZL, Wang JP, Yuan YF, Huang MJ (2005) Hypermethylation of SYK gene in promoter region and its association with invasion in colorectal cancer. Zhong Hua Shi Yan Wai Ke Za Zhi 22(1):68–70

39.

Stewart ZA, Pietenpol JA (2001) Syk: a new player in the field of breast cancer. Breast Cancer Res 3(1):5–7PubMedCrossRef

40.

Calvisi DF, Ladu S, Gorden A, Farina M, Lee JS, Conner EA, Schroeder I, Factor VM, Thorgeirsson SS (2007) Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. J Clin Invest 117:2713–2722PubMedCrossRef

41.

Ehrlich M (2002) DNA methylation in cancer: too much, but also too little. Oncogene 21:5400–5413PubMedCrossRef

42.

Suzuki K, Suzuki I, Leodolter A, Alonso S, Horiuchi S, Yamashita K, Perucho M (2006) Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage. Cancer Cell 9:199–207PubMedCrossRef

43.

Lee S, Lee HJ, Kim JH, Lee HS, Jang JJ, Kang GH (2003) Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis. Am J Pathol 163(4):1371–1378PubMedCrossRef

44.

Sung YM, Xu X, Sun J, Mueller D, Sentissi K, Johnson P, Urbach E, Seillier-Moiseiwitsch F, Johnson MD, Mueller SC (2009) Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo. PLoS One 4(10):e7445

45.

Zhou F, Hu J, Ma H, Harrison ML, Geahlen RL (2006) Nucleocytoplasmic trafficking of the Syk protein tyrosine kinase. Mol Cell Biol 26(9):3478–3491

46.

Bailet O, Fenouille N, Abbe P, Robert G, Rocchi S, Gonthier N, Denoyelle C, Ticchioni M, Ortonne JP, Ballotti R, Deckert M, Tartare-Deckert S (2009) Spleen tyrosine kinase functions as a tumor suppressor in melanoma cells by inducing senescence-like growth arrest. Cancer Res 69(7):2748–2756

Titel: Expression and methylation status of the Syk gene in cervical carcinoma
verfasst von: Shuping Zhao
Guixia Sun
Parks W. Tony
Dehua Ma
Chengquan Zhao
Publikationsdatum: 01.05.2011
Verlag: Springer-Verlag
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 5/2011
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-010-1546-6

Neu im Fachgebiet Gynäkologie und Geburtshilfe

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Expression and methylation status of the Syk gene in cervical carcinoma

Abstract

Objective

Methods

Results

Conclusion

Neu im Fachgebiet Gynäkologie und Geburtshilfe

ICI-Therapie in der Schwangerschaft wird gut toleriert

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

Update Gynäkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

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

Weitere Artikel der Ausgabe 5/2011

Characteristics and prognosis of coexisting adnexa malignancy with endometrial cancer: a single institution review of 51 cases

Erratum to: Laparoscopy-to-laparotomy quotient in obstetrics and gynecology residency programs

The value of spatiotemporal image correlation technique in the diagnosis of fetal ventricular septal defect

Follow-up of dysfunctional bladder and rectum after surgery of a deep infiltrating rectovaginal endometriosis

Laparoscopy-to-laparotomy quotient in obstetrics and gynecology residency programs

Evaluation of ductus venosus and inferior vena cava by using multiple Doppler ultrasound parameters in healthy fetuses

Neu im Fachgebiet Gynäkologie und Geburtshilfe

ICI-Therapie in der Schwangerschaft wird gut toleriert

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

Update Gynäkologie