Oncogenes, vitamin

A large number of proto-oncogenes code for transcription factors required for progression of the cell cycle and/or for the differentiation of the cell. The best known and investigated examples of oncogenic mutated transcription factors involve the jun, fos and myc genes and the genes for the T3 receptor and the vitamin A acid receptor. 

A model of thyroid hormone action is depicted in Figure 38-4, which shows the free forms of thyroid hormones, T4 and T3, dissociated from thyroid-binding proteins, entering the cell by active transport. Within the cell, T4 is converted to T3 by 5 -deiodinase, and the T3 enters the nucleus, where T3 binds to a specific T3 receptor protein, a member of the c-erb oncogene family. (This family also includes the steroid hormone receptors and receptors for vitamins A and D.) The T3 receptor exists in two forms, a and B. Differing concentrations of receptor forms in different tissues may account for variations in T3 effect on different tissues. 

Retinoids in Cancer Prevention and Treatment Since the discovery of vitamin A, the observation that the main effects of deficiency are hyperplasia and loss of differentiation of squamous epithelium has raised speculation that the vitamin may he associated with carcinogenesis. Either deficiency may be a risk factor for cancer or increased intake may be protective. Deficient animals develop more spontaneous tumors and are more sensitive to chemical carcinogens, whereas liver reserves of vitamin A are lower in patients with cancer than in controls. One of the genes repressed by retinoic acid is the myc-oncogene. 

Venkatraman JT, Chu W. Effects of dietary (i)-3 and a)-6 lipids and vitamin E and on proliferative response, lymphoid cell subsets, production of cytokines by spleen cells and splenic protein levels for cytokines and oncogenes in MRL/MpJ-Ipr mice. J Nutr Biochem 1999 10 582-597. 

For vitamin D-resistant rickets, patients can be treated with calcitriol and phosphate supplements. For oncogenic osteomalacia, m-mor resection is best. Otherwise, pharmacologic doses of calcitriol (1.5 to 3 mcg/day) and phosphate supplementation may help. 

Hulia W, Kaliay E, Krugluger W, Peterlik M and Cross HS (1995) Growth control of human colon-adenocarcinoma-derived Caco-2 cells by vita-min-D compounds and extracellular calcium in vitro relation to c-myc-oncogene and vitamin-D-receptor expression. Int J Cancer 62 711-716. 

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