No Effect of the Transforming Growth Factor ¦Â1 Promoter Polymorphism C-509T on TGFB1 Gene Expression, Protein Secretion, or Cellular Radiosensitivity

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• 作者：Sebastian Reuther ; PhD^&lowast ; ; ¹ ; Elisabeth Metzke ; cand.med^&lowast ; ; ¹ ; Michael Bonin ; PhD^&Dagger ; ; Cordula Petersen ; MD^&dagger ; ; Ekkehard Dikomey ; PhD^&lowast ; ; ^{dikomey@uke.de} ; Annette Raabe ; PhD^&lowast ;
• 关键词：Transforming growth factor ¦Â1 ; Polymorphism ; Gene expression ; Protein secretion ; Radiosensitivity
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2013
• 出版时间：1 February, 2013
• 年：2013
• 卷：85
• 期：2
• 页码：460-465
• 全文大小：292 K

文摘

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Purpose

To study whether the promoter polymorphism (C-509T) affects transforming growth factor ¦Â1 gene (TGFB1) expression, protein secretion, and/or cellular radiosensitivity for both human lymphocytes and fibroblasts.

Methods and Materials

Experiments were performed with lymphocytes taken either from 124 breast cancer patients or 59 pairs of normal monozygotic twins. We used 15 normal human primary fibroblast strains as controls. The C-509T genotype was determined by polymerase chain reaction-restriction fragment length polymorphism or TaqMan single nucleotide polymorphism (SNP) genotyping assay. The cellular radiosensitivity of lymphocytes was measured by G0/1 assay and that of fibroblasts by colony assay. The amount of extracellular TGFB1 protein was determined by enzyme-linked immunosorbent assay, and TGFB1 expression was assessed via microarray analysis or reverse transcription-polymerase chain reaction.

Results

The C-509T genotype was found not to be associated with cellular radiosensitivity, neither for lymphocytes (breast cancer patients, P=.811; healthy donors, P=.181) nor for fibroblasts (P=.589). Both TGFB1 expression and TGFB1 protein secretion showed considerable variation, which, however, did not depend on the C-509T genotype (protein secretion: P=.879; gene expression: lymphocytes, P=.134, fibroblasts, P=.605). There was also no general correlation between TGFB1 expression and cellular radiosensitivity (lymphocytes, P=.632; fibroblasts, P=.573).

Conclusion

Our data indicate that any association between the SNP C-509T of TGFB1 and risk of normal tissue toxicity cannot be ascribed to a functional consequence of this SNP, either on the level of gene expression, protein secretion, or cellular radiosensitivity.