Our previous study has indicated that p53 gene mutation occurred in 73% of human functional adrenal
tumors, and the mutation hot spots were focused on
codons 100, 102 (exon 4), and 249 (exon 7). Furthermore, a transcriptional activity study revealed that the mutant p53
protein derived from human functional adrenal
tumors lost 90% transcriptional activity and the ability to bind with the p53 sequence. In order to investigate the influence of the
mutant protein extracted from adrenocortical
tumors on normal adrenal cells, we first cloned p53
cDNA from the human primary
aldosteronism and constituted it with
isopropyl thiogalactoside (
IPTG) inducible expression vector as recombinant plasmid. The recombinant plasmid was then transfected to normal bovine adrenocortical cells through electroporation. The results showed that the p53
protein mutations at
codons 100 and 102 could neither affect the cell morphology nor enable cell growth on the soft
agar. In addition, no significant difference was found in
cortisol level between the p53 transfected and the control cells. On the other hand, cell morphological changes and cell proliferation rate increase were observed when we used
IPTG to induce the expression of the p53
protein, which mutated at
codon 249, in adrenocortical cells. The cell morphology changes included less flattened and decreased elongation when compared to non-transfected cells. However, the
cortisol level in transfected cells was not affected by the p53 mutants. Taken together, we concluded that the mutant p53
protein indeed participates in adrenal
carcinogenesis; however, it has no influence on
hormone production and secretion.