TARGETS FOR THE PREVENTION AND CURE OF FEMALE BREAST CANCER:BC534 AND BC538, TWO RECONSTRUCTED CDNAS AND ENCODED PROTEINS ANTISENSE TO THE HUMAN TUMOUR ANTIGEN P53 GENE

摘要

The human tumour antigen p53, has been definitely implicated as a factor in inherited female breast cancer, but it is also likely to be involved in breast cancer due to acquired mutations. In addition families carrying a mutated p53 gene have an extremely high rate of other cancers including brain tumours and sarcomas. The mode of action of p53 in the pathophysiology of breast cancer is not known. There is no treatment for the disease except surgery. We reconstructed two cDNAs encoding proteins of 21 and 44 amino acids, respectively, which are 100 % homologous to regions on the antisense strand of human p53 gene. The expression of these proteins is repressed by the normal wild type p53 gene healthy in women; however, mutations, inherited or acquired, in regions of the p53 gene which are crucial for maintaining repression could permit the expression of various levels of these two antisense proteins. The antisense proteins are potential intracellular activators of tumour causing and tumour associated proteins and of an inhibitor of 17 .beta. hydroxysteriod interaction with its receptor. The antisense relationship with p53 gene and the functions of these proteins make them ideal candidates for causative factors of p53 related female breast cancer and some other cancers which correlate with this disease in families carrying the mutated p53 gene. Since these proteins are not expressed in normal humans they are excellent targets for developing humanised antibodies against to prevent and cure the disease.