Bcl-2 was first discovered as an oncogene in B cell malignancies. However, it is also expressed in normal lymphoid cells including T-cells. The importance of Bcl-2 for lymphoid development is highlighted by the phenotype of Bcl-2 knockout mice, which display accelerated lymphocyte apoptosis four weeks after birth. Interestingly, Bcl-2 is also expressed in nonlymphoid tissues like the nerve system and epithelium. A potential function of Bcl-2 in neuronal tumours has first been described by Reed et al.. The expression of Bcl-2 in normal epithelium suggests that Bcl-2 may also be expressed in carcinoma. Evidence that Bcl-2 may have oncogenic potential in carcinoma was first provided in prostate cancer, where high expression of Bcl-2 was found in androgen-independent tumours. Since then, high Bcl-2 expression has been reported in many different tumour types including lung cancer, ovary cancer, and breast cancer. The function of Bcl-2 in inhibiting apoptosis has been proven in many independent studies, for example, by overexpression or knockdown. Paradoxically, several studies have reported that high expression of Bcl-2 is not associated with the level of malignancies but may even be associated with favourable prognosis, indicating that, in solid tumours, the role of Bcl-2 as an antiapoptotic gatekeeper is less clear than in haematological malignancies.
Vogler M. Targeting Bcl-2-Proteins for the Treatment of Solid Tumours. Advances in Medicine. 2014;2014:943648.