WWOX: A Fragile Gene on Chromosome 16 Acts as a Tumor Suppressor Gene

Adrezej Bednarek and C. Marcelo Aldaz
University of Texas MD Anderson Cancer Center, Smithfield
P30ES07784

Background: This research team recently reported the cloning of WWOX, a gene in a fragile region of chromosome 16. They observed that the DNA spanned by this gene is affected by chromosomal translocations and homozygous deletions. Allelic loss in this region in breast, ovarian, prostate, and other cancers suggests that WWOX may be a tumor suppressor gene. Further studies on this gene in breast tumor cell lines were conducted to investigate this possibility.

Advance: Growth of the breast tumor cells in vitro was significantly suppressed upon ectopic expression of WWOX. In addition, the WWOX protein dramatically reduces the tumorigenicity of breast cancer cells in vivo. The investigators also found differences in the sequence of the WWOX gene in various carcinoma cell lines, multiple myeloma cell lines, and breast tumors suggesting that these changes in thesequence inactivate the tumor suppressor activity of the gene.

Implication: These findings led the investigators to conclude that WWOX is indeed a potent tumor suppressor gene that is inactivated in several different types of cancer. Additional research with WWOX could have implications on prevention activities and cancer therapies. Scientists may be able to utilize the tumor suppression activity of the gene's products to prevent the formation of tumors or treat them.

Citation: Bednarek AK, Keck-Waggoner CL, Daniel RL, Laflin KJ, Bergsagel PL, Kiguchi K, Brenner AJ, Aldaz CM. WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. Cancer Res. 2001 Nov 15;61(22):8068-73.