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Growth arrest and DNA damage-inducible protein GADD45 alpha (DNA damage-inducible transcript 1 protein) (DDIT-1) [DDIT1] [GADD45]


Differential expression of senescence and cell death factors in non-small cell lung and colorectal tumors showing telomere attrition.

The main aim of this work is to investigate the expression of factors related to senescence and cell death pathways in non-small cell lung cancers (NSCLCs) and colorectal cancers (CRCs) in relation to telomere status. We analyzed 158 tissue samples, 36 NSCLCs, 43 CRCs, and their corresponding control tissues obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. Expression of factors related to senescence, cell death pathways, transformation and tumorigenesis was investigated using arrays. Results were validated by real-time quantitative PCR. Considering tumors with telomere shortening, expression for BNIP3, DAPK1, NDRG1, EGFR, and [[CDKN2A]] was significantly higher in NSCLC than in CRC, whereas TP53 was overexpressed in CRC with respect to NSCLC. Moreover, compared to nontumor samples, DAPK1, GADD45A, SHC1, and TP53 were downregulated in the group of NSCLCs with telomere shortening, and no significant differences were found in CRC. In NSCLC, the failure of pathways which involve factors such as DAPK1, GADD45A, SHC1, and TP53, in response to short telomeres, could promote tumor progression. In CRC, the viability of these pathways in response to short telomeres could contribute to limiting tumorigenesis.

MeSH Terms

  • Adenocarcinoma
  • Aged
  • Aging
  • Biomarkers, Tumor
  • Carcinoma, Large Cell
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Squamous Cell
  • Cell Death
  • Colon
  • Colorectal Neoplasms
  • Female
  • Gene Expression Profiling
  • Humans
  • Lung
  • Lung Neoplasms
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Rectum
  • Telomerase
  • Telomere
  • Telomere Shortening