These findings indicate the role of miR-34a in tumor progression may be closely associated with p53 mutation and inversely correlated to Bcl-2 expression.
With long-term I2, mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased the expression of the apoptotic protein Bax and peroxisome proliferator-activated receptor type gamma.
Our results further revealed that NRP-1 knockdown decreased the expression levels of Bcl-2 family proteins and deactivated extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling pathways, closely associated with cancer progression.
Bcl-2 is a prime target for novel therapeutics because it is elevated in many forms of cancer and contributes to cancer progression and therapy resistance based on its ability to inhibit apoptosis.
The knockdown of XIAP, BCL2 and BCL-X(L) by siRNAs represents a promising treatment option for bladder cancer (BCa) since the overexpression of antiapoptotic genes is often associated with tumor progression and treatment resistance.
These data indicate that the survival requirements for tumor-susceptible PC(pre) and PCs are distinct and that tumor progression likely develops as PC(pre) transition to functional PCs when apoptotic pathways such as members of the Bcl-2 family are disabled.
It is also suggested that the effect of alteration of bcl-2 expression might be minimal during the tumor progression stage because of the reduced expression in tumors of the clear cell type, which is the most dominant cell type in RCC.
To determine whether a specifically designed bispecific (Bcl-2/Bcl-xL) antisense oligonucleotide (ASO) induces apoptosis and enhances chemosensitivity in human prostate cancer LNCaP cells, as Bcl-2 and Bcl-xL are both anti-apoptotic genes associated with treatment resistance and tumour progression in many malignancies, including prostate cancer.
Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure.
Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation.
Thus, acquisition of Bcl-2 expression is as advantageous for tumor cell growth in vivo as is p53 inactivation but does not affect genomic stability and creates the environment restrictive for the expansion of genetically unstable and potentially malignant p53-deficient cells, causing a delay in tumor progression and explaining the different prognostic value of Bcl-2 and p53.
Although cytoplasmic bcl-2 overexpression is found in the majority of tumours in the younger group, it is not associated with tumour progression and recurrence.
This provides evidence that Bcl-2 plays a role in tumor progression of glioma by acting as an oncogene, and suggests that inhibition of the bcl-2 gene could have a therapeutic effect.
In the present study, we investigated the effect of bcl-2 over-expression on the activity of the transcription factor NF-kappaB, an important regulator of genes involved in tumor progression and invasion.
Typically, 1q21-23 rearrangements arise during tumor evolution and accompany disease-specific chromosomal rearrangements such as t(14;18) (BCL2) and t(8;14) (MYC), where they are thus thought to play an important role in tumor progression.
The sequence of mutations in the process of lymphomagenesis seems to be composed of at least 3 main hits which equip the cells with independence from external mitogenic signals (activation of Ras/Raf), resistance to inducers of apoptosis (activation of Bcl-2) and generation of cellular heterogeneity (deletion of p53) important in tumor progression.
Interaction between p53, Bcl-2, and other products of tumor suppressor genes or oncogenes are probably critical in tumor progression and response to treatment.
Altered expression of Bcl-2 family proteins has been associated with tumorigenesis and tumor progression as well as resistance to radiotherapy and chemotherapy.
Bcl-2 plays a role as an inhibitor of apoptosis that may extend the viability of cells containing genetic alterations and facilitate tumor progression.Mutant p53 has a similar effect.