Mutational analysis of the PTEN/MMAC1 tumer suppressor gene in sporadic breast cancers

PTEN (or MMAC1/TEP1) is a tumor suppressor gene that its mutations and deletions were detected in glioma, prostate, melanoma, Endometrium and breast cancers, abundantly. Most mutations occur in exon 5 that codes main domain of PTEN protein. PTEN acts as a lipid phosphate and is regulators of PI3/AKT kinase pathway. PTEN also is a protein phosphate that phosphorelates serine and threonine residues. PTEN with protein-phosphate function plays roles in regulation of several cellular pathways including MAPK. Considering the efficacy of novel drugs (like CCI-779) and therapeutic trials (like rapamycin) demonstrated for breast cancer therapy, influence by the inactivation of PTEN, and high incidence of breast cancer in Isfahan, the potential role of this gene in mammary carcinogenesis was further investigsted. 62 breast cancers were examined for mutations in PTEN/MMAC1 by means of polymerase chain reaction, single-strand conformation polymorphism, heteroduplex and sequencing. According to the results of this research, deletions/insertions and nucleotide changes were found in 2/62 (3%) and 5/62 (8%) of samples, respectively. This rate of mutations in PTEN promises efficacy of new drugs in treatment of patients with breast cancer in Isfahan.