Table 1.
Fold regulations of statistically relevant data obtained in the apoptosis PCR array
| Gene description | Gene symbol | Fold regulation | Category | Expression | Notes |
|---|---|---|---|---|---|
| Tumor necrosis factor (ligand) superfamily, member 10 | TRAIL | 6.7865*** | Anti | Up | It is a cytokine that belongs to the TNF family and is a p53-transcriptional target gene; normally it is involved in tumor cell apoptosis |
| Nucleotide-binding oligomerization domain containing 1 | NOD1 | 3.4806* | Pro | Up | In cell culture experiments, NOD1 has been proven to participate in association with proteins that regulate cell death and it appears to enhance the onset and extent of apoptosis |
| Caspase 8, apoptosis-related cysteine peptidase | CASP8 | 2.1926* | Pro | – | Involved in apoptosis cell signaling |
| Fas (TNF receptor superfamily, member 6) | FAS | 2.0037** | Pro | Up | A member of the TNF-receptor superfamily, it presents a death domain and plays a central role in programmed cell death. It plays an essential role in breast cancer apoptosis induction |
| Caspase 1, apoptosis-related cysteine peptidase | CASP1 | 1.9579*** | Up | Member of the caspase family; it plays an important role in the execution of apoptosis. Due to alternative splicing, it presents many isoforms. In cancer, it is prone to mutations | |
| Caspase recruitment domain family, member 8 | CARD8 | 1.9399* | Pro | Up | It was found to be overexpressed in breast cancer cell lines, but not in breast tumors. It is involved in NF-κB signaling associated with innate or adaptive immune response and plays an important in apoptosis regulation |
| Tumor protein p53-binding protein 2 | TP53BP2 | 1.8738** | Pro | Down | It promotes apoptosis through a p53-mediated mechanism. It was also proved to bind other proteins like BCL-2 and NF-κB, and there are evidences that indicate its involvement in the intrinsic apoptosis pathway |
| BCL2-associated athanogene | BAG1 | 1.8226* | – | Up | In breast cancer, the upregulation of this gene was associated with a low survival rate. It was observed to be implicated in tumor development and is associated with a high risk of developing metastatic disease |
| Baculoviral IAP repeat containing 3 | BIRC3 | 1.6238* | Anti | – | Antiapoptotic factor that stimulates tumor cell survival through binding to the TRAF1- and TRAF2-associated factors of the TNF receptors 1 and 2. Probably inhibits cell apoptosis through inhibiting caspase activation |
| NLR family, apoptosis inhibitory protein | NAIP | 1.6125* | – | Up | Involved in the progression of breast cancer, with no direct involvement in the apoptotic pathways |
| Caspase recruitment domain family, member 6 | CARD6 | 1.522** | Anti | – | Involved in NF-κB pathway activation through various independent pathways. Implicated in the immune response |
| BCL2/adenovirus E1B 19 kDa interacting protein 2 | BNIP2 | −1.6029* | Pro | – | Is a member of the BCL-2 family involved in the mitochondrion-mediated apoptosis that represents the main mechanism involved in chemotherapeutic-induced apoptosis |
| BCL2-antagonist/killer 1 | BAK1 | −1.754* | Pro | Down | A proapoptotic protein from the BCL-2 family involved in the intrinsic apoptosis pathway |
| Tumor necrosis factor | TNF | −1.7909* | Pro/anti | – | A multifunctional cytokine and cell receptor ligand that plays a dual role in receptor-mediated apoptosis and cell survival |
| Tumor protein p53 | TP53 | −3.0823** | Pro | – | Tumor suppressor gene involved in DNA repair through cell cycle arrest or apoptosis as a response to DNA damage. In 50% of the cancers, the p53 gene is mutant, presenting a lack of function or a partial function |
Notes: Role of the genes in breast cancer that present significant difference in mRNA expression after siRNA mut-p53 and TNF transfection in Hs578T cell line. P-value is represented as
*
P≤0.05,
**
P≤0.01,
***
P≤0.001. The biological function, pro- or antiapoptotic activity, and the comments listed in the table are based on our findings and in concordance with the breast cancer literature in the field (data found in atlasgeneticsoncology.org).
Abbreviations: mRNA, messenger RNA; NF-κB, nuclear factor-kappa B; PCR, polymerase chain reaction; siRNA, small interfering RNA; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; ‘–’, no data.