TGF-β polymorphism and its expression correlated with CXCR4 expression in human breast cancer.

Julie Massayo Maeda Oda, Karen Brajão de Oliveira, Roberta Losi Guembarovski, Kalil William Alves de Lima, Ana Cristina da Silva do Amaral Herrera, Alda Losi Guembarovski, Walter Jorge Sobrinho, Daniela Rudgeri Derossi, Maria Angelica Ehara Watanabe
Author Information
  1. Julie Massayo Maeda Oda: Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, PR, CEP 86051-990, Brazil.

Abstract

The role of chemokines and the growth factors has been extensively analyzed both in cancer risk and tumor progression. The transforming growth factor beta (TGF-β) and chemokine (C-X-C motif) receptor 4 (CXCR4) genes are implicated in several diseases, including breast cancer. Genomic DNA was obtained from 21 samples of peripheral blood or from normal tissue, previously fixed in formalin and embedded in paraffin for TGF-β T869C polymorphism analyses. Total cellular RNA was extracted from the same 21 patients, but from fresh tissue (tumor and adjacent healthy from the same breast) for expression analysis by Real Time PCR. No significant differences were observed in genotype distribution according to clinicopathological characteristics. Transforming growth factor beta (TGF-β) mRNA expression was assessed according to T869C polymorphism and CC patients presented a higher TGF-β expression but not significant when compared to other genotypes (p = 0.064). A positive correlation was observed in relative mRNA expressions of CXCR4 and TGF-β (p = 0.020). It is known that overexpression of TGF-β by both tumor and stromal tissue can facilitate the development of metastases, mainly by TGF-β stimulated angiogenesis and increased tumor cell motility. Our findings suggested a role of these genes as progression markers for breast carcinoma.

References

  1. Ann N Y Acad Sci. 2010 Jun;1197:158-65 [PMID: 20536845]
  2. Breast Cancer Res Treat. 2005 Mar;90(2):149-55 [PMID: 15803361]
  3. Breast Cancer Res. 2000;2(2):125-32 [PMID: 11250702]
  4. Cytokine Growth Factor Rev. 2010 Feb;21(1):49-59 [PMID: 20018551]
  5. J Cancer Res Clin Oncol. 2009 Aug;135(8):997-1004 [PMID: 19125297]
  6. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3479-84 [PMID: 10725360]
  7. Circulation. 2000 Jun 20;101(24):2783-7 [PMID: 10859282]
  8. Cancer Res. 2008 Mar 15;68(6):1809-19 [PMID: 18339861]
  9. Endocrine. 2000 Aug;13(1):1-10 [PMID: 11051041]
  10. Nucleic Acids Res. 2001 May 1;29(9):e45 [PMID: 11328886]
  11. Breast Cancer. 2003;10(1):63-9 [PMID: 12525765]
  12. Blood Cells Mol Dis. 2005 Sep-Oct;35(2):286-90 [PMID: 16027015]
  13. Cell Cycle. 2009 Oct 15;8(20):3319-27 [PMID: 19806012]
  14. J Soc Integr Oncol. 2008 Fall;6(4):158-68 [PMID: 19134448]
  15. Annu Rev Immunol. 2006;24:99-146 [PMID: 16551245]
  16. Cancer Epidemiol Biomarkers Prev. 2004 Mar;13(3):412-5 [PMID: 15006917]
  17. Trends Cell Biol. 2001 Nov;11(11):S44-51 [PMID: 11684442]
  18. Br J Cancer. 1993 Jun;67(6):1408-12 [PMID: 8390290]
  19. Am J Pathol. 1994 Dec;145(6):1301-8 [PMID: 7992835]
  20. Cancer Lett. 2011 Aug 28;307(2):132-40 [PMID: 21530075]
  21. Cancer Res. 2006 Nov 15;66(22):10861-9 [PMID: 17090522]
  22. Calcif Tissue Int. 2001 Dec;69(6):315-20 [PMID: 11800227]
  23. Br J Cancer. 2008 Oct 21;99(8):1357-63 [PMID: 18827819]
  24. Cancer Res. 2003 May 15;63(10):2610-5 [PMID: 12750287]
  25. Endocr Relat Cancer. 2004 Sep;11(3):497-522 [PMID: 15369451]
  26. Stem Cells. 2005 Aug;23(7):879-94 [PMID: 15888687]
  27. Clin Cancer Res. 2009 Apr 1;15(7):2302-10 [PMID: 19318481]
  28. Breast Cancer Res. 2005;7(4):R402-10 [PMID: 15987445]
  29. Acta Pharmacol Sin. 2010 Mar;31(3):347-54 [PMID: 20154716]
  30. J Biol Chem. 2010 May 7;285(19):14747-55 [PMID: 20207742]
  31. Cancer Res. 2006 Apr 15;66(8):4117-24 [PMID: 16618732]

MeSH Term

Biomarkers, Tumor
Breast Neoplasms
Carcinoma, Ductal, Breast
Female
Gene Expression
Genetic Association Studies
Humans
Polymorphism, Single Nucleotide
RNA, Messenger
Receptors, CXCR4
Sequence Analysis, DNA
Transforming Growth Factor beta1

Chemicals

Biomarkers, Tumor
CXCR4 protein, human
RNA, Messenger
Receptors, CXCR4
TGFB1 protein, human
Transforming Growth Factor beta1

Word Cloud

Created with Highcharts 10.0.0TGF-βexpressiontumorbreastgrowthcancerCXCR4tissuepolymorphismroleprogressionfactorbetagenes21T869CpatientssignificantobservedaccordingmRNAp=0chemokinesfactorsextensivelyanalyzedrisktransformingchemokineC-X-Cmotifreceptor4implicatedseveraldiseasesincludingGenomicDNAobtainedsamplesperipheralbloodnormalpreviouslyfixedformalinembeddedparaffinanalysesTotalcellularRNAextractedfreshadjacenthealthyanalysisRealTimePCRdifferencesgenotypedistributionclinicopathologicalcharacteristicsTransformingassessedCCpresentedhighercomparedgenotypes064positivecorrelationrelativeexpressions020knownoverexpressionstromalcanfacilitatedevelopmentmetastasesmainlystimulatedangiogenesisincreasedcellmotilityfindingssuggestedmarkerscarcinomacorrelatedhuman

Similar Articles

Cited By