CXCL12, CXCR4 and IFNγ genes expression: implications for proinflammatory microenvironment of breast cancer.
Signals from the microenvironment have a profound influence on the maintenance or progression of breast cancer. In the present study, the frequency of CXCL12 rs1801157 polymorphism in peripheral blood and the expression of CXCL12, CXCR4 and IFNγ mRNA in normal and mammary gland tumor tissues were assessed in breast cancer patients. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism and expression analyses by quantitative RT-PCR. A lower CXCL12 mRNA relative expression was observed among allele A carriers when compared to GG carriers (p = 0.012). ER-positive breast cancer allele A carriers showed a significantly lower expression of CXCL12 mRNA within tumor tissue than in normal breast tissue when compared to GG ER-positive patients (p = 0.016). CXCR4 mRNA (p < 0.001) and CXCL12 mRNA (p = 0.02) relative expressions were significantly correlated with relative IFNγ mRNA expression. Allele A carriers presenting high levels of IFNγ had a significantly higher expression of CXCR4 mRNA in tumor tissue than GG patients (p = 0.026). It is possible that allele A carrier hormone receptor-positive patients could be more susceptible to metastasis development, since they present a lower CXCL12 expression in tumor tissue, and tumor cells expressing CXCR4 could migrate toward CXCL12 gradient. IFNγ expression increases in order to improve immune response and could favor higher CXCR4 expression leading to migration of cells, possibly of metastatic ones, too.
Department of Pathological Sciences, Laboratory of Molecular Genetic- Immunology, Biological Sciences Center, State University of Londrina, Londrina, PR, Brazil.
Karen Brajão
KB
de Oliveira
Roberta Losi
RL
Guembarovski
Alda Maria Fiorina Losi
AM
Guembarovski
Ana Cristina
AC
da Silva do Amaral Herrera
Walter Jorge
WJ
Sobrinho
Carolina Batista
CB
Ariza
Maria Angelica Ehara
MA
Watanabe
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D007371:Interferon-gamma