Genes most commonly associated with the process of oncogenesis include: p53 inactivating mutation; hDM2 overexpression; p16 reduced expression; K-/H-RAS activating mutation; PTEN inactivating mutation/deletion; EGFR activating mutation and overexpression; retinoblastoma inactivating mutation and deletion; Cyclin proteins overexpression; CD95 reduced expression; protective BCL-2 proteins overexpression; to name but just a few of such molecules.
The bcl-2 proto-oncogene is centrally involved in the oncogenesis of human follicular lymphoma via a chromosomal translocation t(14;18)(q32;q21) and is also expressed in the epithelial regenerative compartment or the basal crypts of the normal colon and small intestine.
We developed a new in vivo selection system with the non-phosphorylatable Bcl2 mutant Bcl2<sup>T69A/S70A/S87A</sup> (Bcl2<sup>AAA</sup>), which makes in vivo selection drug independent and without risk of cytotoxicity or tumorigenesis.
Results have made it clear that a number of coordinating alterations in the BCL2 family of genes must occur to inhibit apoptosis and provoke carcinogenesis in a wide variety of cancers.
Bcl-2 and MALT1 genes are located at or near the translocation breakpoints, and the aim of this study was to determine whether these genes were involved in chromosomal translocation or tumorigenesis.
The development of follicular lymphoma (FL) from a founder B cell with an upregulation of B-cell lymphoma 2 (BCL2), via the t(14;18) translocation, to a proliferating clone, poised to undergo further transformation to an aggressive lymphoma, illustrates the opportunistic Darwinian process of tumorigenesis.
Oncogenic changes of bcl-2 and p53 may play a role in tumorigenesis of gallbladder carcinoma, but such changes were not correlated with spontaneous apoptosis.
Together, these results suggest that miR-21 functions as an oncogene and modulates tumorigenesis through regulation of genes such as bcl-2 and thus, it may serve as a novel therapeutic target.
Thus, Bcl-2 may play a very important role in carcinogenesis of gastric cancer and its knockdown may offer a new potential gene therapy approach for human gastric cancer in future.
This review will focus on the role of Bcl-2 family proteins in normal breast development, breast tumorigenesis and acquired resistance to breast cancer treatment strategies, while highlighting Mcl-1 as a promising target to improve breast cancer tumor cell killing.
Our study shows that a low expression of bcl-2 characterises most Brca1 -associated breast carcinomas, a biological trait which seems not to be shared by Brca2 -associated tumours nor to be related to oestrogen receptor and/or p53 status. bcl-2 might thus be one of the target genes involved in the oncogenesis related to Brca1 and its down-regulation may account for the increased apoptosis and the high proliferative rate observed in Brca1 -associated carcinomas.
Gain of Bcl-2 function in mammary epithelial cells was superimposed on the WAP-TAg transgenic mouse model of breast cancer progression to determine its effect on epithelial cell survival and proliferation at three key stages in oncogenesis: the initial proliferative process, hyperplasia, and cancer.
Together, these data suggest a context-dependent phenotypic function of Bcl-2 in the regulation of overlapping cell fate specification programs, with potential implications for both physiology and multistep tumorigenesis.
The expression of HOXC5, proliferation cell nuclear antigen (PCNA), and Bcl-2 was examined by RT-PCR and Western blot analysis and confirmed by immunohistochemistry and transferase-mediated dUTP nick end-labeling (TUNEL) assay in a 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis model.
Because the Cdx1 homeobox gene stimulates proliferation and induces transformation and tumorigenesis, it has been investigated whether it is involved in the complex network comprising p53, p21(WAF), and Bcl-2 in intestinal epithelial cells.