Microarray analysis of formalin-fixed paraffin-embedded specimens shows distinct gene expression patterns in tumors containing the transforming growth factor beta receptor 6A polymorphism (TGFBR1*6A)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4111-4111
Author(s):  
A. Omori ◽  
C. Stephens ◽  
J. Cooc ◽  
P. V. Danenberg ◽  
K. Danenberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Differentially Expressed Genes ◽  
Microarray Analysis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Colorectal Tumors ◽  
Metastatic Tumors ◽  
Exon 1 ◽  
Growth Factor Beta

4111 Introduction: A frequent polymorphism of the type I transforming growth factor beta receptor (TGFBR1) is TGFBR1*6A (6A), which has a deletion of 3 CGC triplets coding for alanine within a 9-alanine (9A) repeat of TGFBR1 exon 1. 6A may act as a tumor susceptibility allele through switching TGF-beta growth inhibitory signals into growth stimulatory signals and also appears to be acquired in some cases by primary colon cancers and their liver metastases. Our aim in this study was to compare the gene expression profiles of colorectal tumors bearing the 6A and the more common 9A genotypes to discover pathways that might be differentially induced by the 6A polymorphism. Methods: 28 colorectal tumors with matched synchronous metastases and 23 non-metastatic colorectal tumors were analyzed for TGFBR1 exon 1 genotype by a PCR-based assay. Nine metastatic and 10 non-metastatic tumors were analyzed by gene expression microarrays. Following microdissection of paraffin-embedded specimens, RNA was isolated, amplified, labeled, and hybridized to Affymetrix U133 Plus 2.0 GeneChips. Results: Among the 28 primary metastatic tumors, 19 were 9A (68%), 8 were 9A/6A heterozygotes (29%) and 1 was a 6A homozygote (3%). There was 100% genotype correspondence with the matched metastases. Among the 23 non-metastatic tumors, 18 were 9A (78%), 3 were heterozygotes (13%) and 2 were 6A/6A (9%). Microarray analysis showed 578 differentially expressed genes in the metastatic tumors and 467 in the non-metastatic tumors between the 6A and 9A genotypes (p<0.01). Significant pathway deregulation between 9A and 6A genotypes included estrogen receptor signaling and histidine metabolism in the non-metastatic tumors and B cell receptor, GM-CSF, SAPK/JNK and IL-4 signaling in the metastatic tumors. Conclusion: Microarray analysis shows differentially expressed genes in the 6A genotype compared to 9A, with different deregulated pathways in metastatic and non-metastatic tumors. This alludes to 6A-specific downstream signaling effects, which may contribute to tumor development and progression. No significant financial relationships to disclose.

Transcriptional modulation of transin gene expression by epidermal growth factor and transforming growth factor beta

1988 ◽  
Vol 8 (6) ◽  
pp. 2479-2483
Author(s):  
C M Machida ◽  
L L Muldoon ◽  
K D Rodland ◽  
B E Magun
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Prolonged Treatment ◽  
Transcriptional Level ◽  
Tgf Beta ◽  
Epidermal Growth ◽  
Growth Factor Beta

Transin is a transformation-associated gene which is expressed constitutively in rat fibroblasts transformed by a variety of oncogenes and in malignant mouse skin carcinomas but not benign papillomas or normal skin. It has been demonstrated that, in nontransformed Rat-1 cells, transin RNA expression is modulated positively by epidermal growth factor (EGF) and negatively by transforming growth factor beta (TGF-beta); other peptide growth factors were found to have no effect on transin expression. Results presented here indicate that both protein synthesis and continuous occupancy of the EGF receptor by EGF were required for sustained induction of transin RNA. Treatment with TGF-beta inhibited the ability of EGF to induce transin, whether assayed at the transcriptional level by nuclear run-on analysis or at the level of transin RNA accumulation by Northern (RNA) blot analysis of cellular RNA. TGF-beta both blocked initial induction of transin transcription by EGF and halted established production of transin transcripts during prolonged treatment. These results suggest that TGF-beta acts at the transcriptional level to antagonize EGF-mediated induction of transin gene expression.

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