Oncogenes: Bcl-2

Bcl-2 (for B cell lymphoma gene-2) proteins are associated with membranes and membrane activity. The Bcl-2 protein is a part of a complex system of signaling that controls apoptosis. Apoptosis (cell death) may be induced by a variety of signals including irreparable DNA damage. This form of cellular suicide prevents the expansion of damaged cells. Bcl-2 works to prevent apoptosis.⁽¹⁾ Therefore, its overexpression can prevent apoptosis in cells that are damaged. This can lead to the continued division of the mutated cells lines and eventually cancer. Also, overexpression of Bcl-2 can contribute to metastasis in certain cancers.⁽²⁾

If apoptosis controls are disrupted, then drugs that work by inducing apoptosis will not work as efficiently. Therefore, drugs are being developed that will down-regulate Bcl-2 and allow other anti-cancer drugs to work more efficiently (and at lower doses). One such drug is the antisense nucleotide Genasense", which has shown in phase I trials to reduce Bcl-2 production and is currently in phase II and III trials as a supplementary treatment for various cancers.⁽³⁾ More on antisense drugs.

Also, there are drugs that indirectly reduce the amount of Bcl-2 protein, such as all-trans retinoic acid, paclitaxel, vincristine, and docetaxel. These drugs are are often combined with other chemotherapy agents during treatment. New methods, not yet tested in humans, include Bcl-2 binding peptides that inactivate the protein and antimycin A that binds to Bcl-2 related proteins. ⁽⁴⁾

Since Bcl-2 overexpression can affect the success of cancer treatment, knowing if it is functioning normally may prove to be a valuable diagnostic tool. This proto-oncogene can become activated into an oncogene by a translocation that causes overexpression of the gene, and an increased amount of Bcl-2 protein has been discovered in many different types of cancers.⁽⁵⁾

1. Strasser A, Huang DC, Vaux DL. "The role of the bcl-2/ced-9 gene family in cancer and general implications of defects in cell death control for tumourigenesis and resistance to chemotherapy." Biochim Biophys Acta. 1997 Oct 24;1333(2):F151-78. [PUBMED]
2. Fernandez Y, Gu B, Martinez A, Torregrosa A, Sierra A. "Inhibition of Apoptosis in Human Breast Cancer Cells: Role in Tumor Progression to the Metastatic State." Int. J. Cancer (2002). 101: 317-326. [PUBMED]
3. Genta Pharmaceuticals [http://www.genta.com]
4. Obasaju C, Hudes GR. "Paclitaxel and docetaxel in prostate cancer." Hematol Oncol Clin North Am. 2001 Jun;15(3):525-45. [PUBMED]
5. Gross A. "BCL-2 proteins: regulators of the mitochondrial apoptotic program." IUBMB Life. 2001 Sep-Nov;52(3-5):231-6. [PUBMED]