Relationship Between PTEN And PI3K/AKT Signaling Pathway In Invasive Breast Cancer

Objective:Breast cancer is one of the serious malignant tumors that threatens women’s health.According to global data there are more than 1.2 million newly-increased breast cancer patients every year,and the annual deaths are about 500,000.In large and medium-sized cities in China,the incidence of breast cancer has become a common malignancy for women.In the first place,the prognosis of breast cancer is poor,and the recurrence and distant metastasis of breast cancer are the major causes of poor prognosis among many factors that affect prognosis.The PTEN gene was a new tumor suppressor gene discovered in 1997.The main functional domain of the PTEN protein is located at the N-terminus and consists of a polypeptide chain consisting of 403 amino acids encoded by 1209 nucleotides.Its 122-133 amino acid sequence corresponds to the core sequence of the protein tyrosine phosphatase and the dual-specificity phosphatase catalytic domain,and it is the first tumor suppressor gene with phosphatase activity discovered so far.The N-terminus of PTEN also has a sequence homologous to cellular Auxilin protein and tension protein,the former being related to the transport of synaptic vesicles,which is a cytoskeletal protein that forms with actin filaments when cells aggregate and adhere.This complex contains many substances,such as focal adhesion kinase(FAK),growth factor receptors and integrins.Integrins are not only related to cell growth regulation,but also to tumor invasion and metastasis.Angiogenesis is involved.Therefore,it is speculated that the function of PTEN gene may also be related to focal adhesion complexes,and by adjusting the biological function of one or more of these substances,tumor inhibition can be achieved.Phosphatidylinositol 3-kinase(PI3K)is an important member of the phospholipase kinase family and consists of a p110 catalytic subunit and p85 regulatory subunit.It has lipid kinase activity and serine/threonine protein kinase activity,and can be used for many purposes.Various cytokine receptors,including tyrosine kinase receptors,non-tyrosine kinase receptors,etc.are activated.The protein encoded by the Akt oncogene has a serine/threonine kinase activity,and its amino acid sequence in the kinase active region is highly homologous to protein kinase A(PKA)and C(PKC),and is also known as PKB.When the growth factor binds to the corresponding receptor,phosphorylation occurs in the intracellular domain of the receptor.The p85 regulatory subunit of PI3 K binds to phosphorylated receptors via the SH2 domain,releasing the inhibitory effect on the p110 catalytic subunit,leading to PI3 K activation.Phosphatidylinositol 2-phosphate(PIP2)and PIP3 were catalyzed by the activated PI3 K from the phosphorylation of phosphatidylinositol(PI).PIP3 as a second messenger recruits Akt and phosphoinositide dependent kinase(PDK)to the membrane region.Phosphorylation of PDK activates Thr308 and ser473 of Akt and induces subsequent cascade reactions.To explore the expression of tumor suppressor gene PTEN in human breast cancer and normal breast tissue and its possible mechanism.Methods:The expression of PTEN protein and mRNA in 60 cases of breast cancer and 30 cases of normal breast tissues were detected by immunohistochemical SP method and Western blot.The correlation between the expression of PTEN protein and Akt and P-Akt was analyzed by two independent samples t test Statistical analysis.Results:The results of immunohistochemistry showed that the positive rate of PTEN in breast cancer tissues(20%)was significantly lower than that of normal breast tissues(60%)(P<0.05).Western blot analysis showed that PTEN protein was detected in breast cancer.The relative expression levels in the normal and breast tissues were 0.87 ± 0.06,1.38 ± 0.16,respectively.There was a statistically significant difference between the two groups(P<0.05).In 60 breast cancer tissues,the relative expression of P-Akt in the PTEN-positive group was 0.98±0.07,which was significantly lower than that in the negative group(1.76±0.21)(P<0.05).There was a significant difference between the two groups(P<0.05).There was no significant difference in the relative expression of Akt between the two groups.Conclusion:More positive PTEN protein expression was detected in normal breast tissue relative to cancer tissue,suggesting that PTEN is closely related to the progression of breast cancer.It is speculated that PTEN may be used as an indicator to predict the prognosis and survival of breast cancer patients;PTEN expression and P-Akt The expression was negatively correlated,suggesting that PTEN may regulate the invasion and metastasis mechanism of breast cancer by regulating the PI3K/AKT pathway.