Properties of Human Tumor Suppressor 101F6 Protein as a Cytochrome b561 and Its Preliminary Crystallization Trials

Identification of the physiological roles and elucidation of the molecular mechanisms involving tumor suppressor genes and their gene products are important for a more comprehensive understanding of cancer pathogenesis. Since the Knudson’s statistical studies on retinoblastoma, neuroblastoma, and pheochromocytoma, which led to the conclusion that the occurrence of these tumors fits a two-mutation model (Knudson, 1971; Knudson & Strong, 1972), it became recognized that there were some genes that function to inhibit tumor development. The model stated that tumorigenesis results when there are genetic alterations such as deletions and mutations in both alleles of a gene in a cell (Knudson, 1971; Knudson & Strong, 1972). A tumor suppressor gene may have one or more functions related to cell division and differentiation, extracellular communication, tissue formation or senescence (Hollingsworth & Lee, 1991). Several regions of the human chromosome 3 have been identified as susceptible sites for homozygous deletions and mutations that may lead to inactivation of one or more tumor suppressor genes. A particular tumor suppressor gene candidate 101F6 is located within a narrow 630-kb region on chromosome 3p.21.3, called LUCA (lung cancer region) (Lerman & Minna, 2000; Zabarovsky et al., 2002). Interestingly, the 101F6 protein is expressed in normal lung bronchial epithelial cells and fibroblasts but is lost in most lung cancers (Ohtani et al., 2007). Previous studies have shown that forced expression of the 101F6 gene via adenoviral vector-mediated gene transfer (Ji et al., 2002) or via nanoparticle injection (Ohtani et al., 2007) caused the inhibition of tumor growth in non-small cell lung cancer cells in vitro and in vivo. The treated cancer cells were also found to accumulate ascorbate (AsA) when incubated in a medium containing AsA (Ohtani et al., 2007). Apoptosis and autophagy of the cancer cells were reportedly to be enhanced by the treatment and were postulated to be caused by the synergistic action of the 101F6 gene and AsA though the mechanism of the action is still not clear (Ohtani et al., 2007).