Transforming Growth Factor Alpha Taq I Polymorphisms and Nonsyndromic Cleft Lip and/or Palate Risk

2018 ◽  
Vol 55 (6) ◽  
pp. 814-820 ◽  
Author(s):  
Chen Yan ◽  
He Deng-qi ◽  
Chen Li-ya ◽  
Yang Mang ◽  
Yang Ke-hu
Keyword(s):  
Growth Factor ◽  
Confidence Intervals ◽  
Odds Ratio ◽  
Cleft Lip ◽  
Transforming Growth Factor ◽  
Meta Analysis ◽  
Biomedical Literature ◽  
Transforming Growth Factor Alpha ◽  
Wild Type ◽  
Factor Alpha

Background: A series of epidemiological studies were conducted to investigate the association between transforming growth factor alpha ( TGFA) polymorphism and nonsyndromic cleft lip and/or palate (CL/P) risk, but the findings remain conflicting. The present meta-analysis summarizes the association between the TGFA Taq I polymorphisms and nonsyndromic CL/P risk. Methods: We searched PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature databases from their inception to May 1, 2015. Fixed-effects or random-effects models were used to calculate the pooled odds ratio for two genetic comparisons (heterozygous mutation versus wild type, homozygous mutation versus wild type). All of the statistical tests were conducted by STATA 10.0 (StataCorp, College Station, TX). Results: A total of 26 case-control studies were identified for this meta-analysis. There was evidence of a significant association between the TGFA Taq I polymorphism and nonsyndromic CL/P risk in the overall population. The TGFA polymorphism was associated with nonsyndromic CL/P susceptibility in Asian populations under any of genetic models. However, in subgroup analysis, we did not find a significant association of TGFA gene polymorphisms with a reduced cancer risk in White and other populations and (recessive model, odds ratio = 2.37, 95% confidence intervals = 0.92-6.07; odds ratio = 3.45, 95% confidence intervals = 1.07-11.09, respectively). Conclusion: Our study indicates that the TGFA gene polymorphism might be associated with nonsyndromic CL/P susceptibility. However, these findings still need to be confirmed by single, large, well-designed prospective studies.

scholarly journals p53 stimulates transcription from the human transforming growth factor alpha promoter: a potential growth-stimulatory role for p53.

1995 ◽  
Vol 15 (9) ◽  
pp. 4694-4701 ◽  
Author(s):  
T H Shin ◽  
A J Paterson ◽  
J E Kudlow
Keyword(s):  
Growth Factor ◽  
Binding Site ◽  
Proliferative Response ◽  
Transforming Growth Factor ◽  
Tata Box ◽  
Stable Cell Line ◽  
Protective Mechanism ◽  
Transforming Growth Factor Alpha ◽  
Wild Type ◽  
Factor Alpha

Physical and chemical agents can damage the genome. Part of the protective response to this damage is the increased expression of p53. p53, a transcription factor, controls the expression of genes, leading to cell cycle arrest and apoptosis. Another protective mechanism is the proliferative response required to replace the damaged cells. This proliferation is likely to be signaled by growth factors. In this communication, we show that the transforming growth factor alpha (TGF-alpha) gene is a direct target for p53-mediated transcriptional activation. In a stable cell line containing an inducible p53 construct, p53 induction leads to a threefold accumulation of the native TGF-alpha mRNA. IN cotransfection assays using a TGF-alpha promoter reporter construct, we show that expression of wild-type but not mutant p53 increases transcriptional activity of the TGF-alpha promoter by approximately 2.5-fold. In vitro, wild-type p53 binds to a consensus binding site found in the proximal portion of the promoter, and this sequence is necessary for the p53 transcriptional response. Furthermore, this element confers p53 induction to the otherwise nonresponsive adenovirus major late promoter. In addition to these results, we found that the TGF-alpha promoter contains a nonconsensus but functional TATA box-binding protein-binding site approximately 30 bp upstream of the transcription start site. Although p53 can repress transcription from promoters containing a TATA box, the nonconsensus TGF-alpha TATA motif is resistant to this effect. On the basis of these results, we propose that p53 may play a dual role, which includes both the elimination of irreparably genetically damage cells and the proliferative response necessary for their replacement, in the response to physical-chemical damage.

scholarly journals Transforming growth factor-alpha and beta-amyloid precursor protein share a secretory mechanism.

1995 ◽  
Vol 128 (3) ◽  
pp. 433-441 ◽  
Author(s):  
J Arribas ◽  
J Massagué
Keyword(s):  
Growth Factor ◽  
Membrane Protein ◽  
Cell Surface ◽  
Cho Cells ◽  
Transforming Growth Factor ◽  
Surface Proteins ◽  
Transforming Growth Factor Alpha ◽  
Wild Type ◽  
Cell Surface Proteins ◽  
Factor Alpha

Cleavage and release of membrane protein ectodomains, a regulated process that affects many cell surface proteins, remains largely uncharacterized. To investigate whether cell surface proteins are cleaved through a shared mechanism or through multiple independent mechanisms, we mutagenized Chinese hamster ovary (CHO) cells and selected clones that were unable to cleave membrane-anchored transforming growth factor alpha (TGF-alpha). The defect in TGF-alpha cleavage in these clones is most apparent upon cell treatment with the protein kinase C (PKC) activator PMA, which stimulates TGF-alpha cleavage in wild-type cells. The mutant clones do not have defects in TFG-alpha expression, transport to the cell surface or turnover. Concomitant with the loss of TGF-alpha cleavage, these clones have lost the ability to cleave many structurally unrelated membrane proteins in response to PMA. These proteins include beta-amyloid precursor protein (beta-APP), whose cleavage into a secreted form avoids conversion into the amyloidogenic peptide A beta, and a group of cell surface proteins whose release into the medium is stimulated by PMA in wild type CHO cells but not in mutants. The mutations prevent cleavage by PKC-dependent as well as PKC-independent mechanisms, and thus affect an essential component that functions downstream of these various signaling mechanisms. We propose that regulated cleavage and secretion of membrane protein ectodomains is mediated by a common system whose components respond to multiple activators and act on susceptible proteins of diverse structure and function.

No Evidence of Linkage for Cleft Lip with or without Cleft Palate to a Marker Near the Transforming Growth Factor Alpha Locus in Two Populations

1997 ◽  
Vol 47 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Diego F. Wyszynski ◽  
Nancy Maestri ◽  
Amy F. Lewanda ◽  
Iain McIntosh ◽  
Anne Smith ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha ◽  
Two Populations

Association between alleles of the transforming growth factor-alpha locus and the occurrence of cleft lip

1993 ◽  
Vol 45 (5) ◽  
pp. 565-569 ◽  
Author(s):  
Russell Sassani ◽  
Scott P. Bartlett ◽  
Hongshu Feng ◽  
Audrey Goldner-Sauve ◽  
Asifa K. Haq ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cleft Lip ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha
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