Expression Of Amino Acid Transporter LAT1,ATB^0,+ And PTEN In Breast Cancer And Their Relationship To Drug Resistance

Objective:Tumor cells tend to proliferate rapidly in human bodies which upregulates specific amino acid transporters,among which,LAT1?large amino acid transporter 1?and ATB^0,+?amino acid transporter?stand out with specific functional features of holding great potential for tumor-selective drug delivery.This study combined the expression of LAT1,ATB^0,+and the tumor suppressor gene PTEN with the resistance to chemotherapeutic drugs in breast cancer tissues.Based on high expression of two amino acid transporters LAT1 and ATB^0,+which are on the surface of mammary gland tumor cells,the purpose of this study was to investigate the relationship between the expression of LAT1,ATB^0,+and the tumor suppressor gene PTEN in breast tumor tissues with the situation of valid and invalid to chemotherapeutic drugs,and its underlying clinical significance,and provided theoretical reference for the construction of double breast tumor targeted nanoparticles.Methods:1.This study collected 164 breast cancer patients'clinical significance and analyzed the correlation between the expression of LAT1,ATB^0,+and PTEN by immunohistochemistry.Patients were divided into a chemotherapeutic-drug-resistant group and a drug-sensitive group according to the evaluation standard of RICIST,MP?Miller-Payne?and RCB?Residual Cancer Burden?.2.We analyzed the correlation between the expression of LAT1,ATB^0,+and PTEN by Western blot?WB?in 30 breast cancer puncture specimens before neoadjuvant chemotherapy.3.We examined the expression position of amino acid transporter LAT1,ATB^0,+protein by Immunofluorescence?IF?.4.Statistical analysis:SPSS22.0 statistical software package was used for t-test,Pearson chi-square test,Fisher precision calculation probability method and Spearman rank correlation test.P<0.05 was statistically significant.Results:1.ImmunofluorescenceexperimentsuggestedLAT1,ATB^0,+as transmembrane proteins mainly distributed in the cell membrane and cytoplasm of breast cancer cells.2.Western Blot experiment suggested that the expressions of LAT1,ATB^0,+and PTEN were significantly increased in the chemotherapy effective group,P?LAT1?=0.008,P(ATB^0,+)=0.029,P?PTEN?=0.016.3.The 164breast cancer patients were divided into a chemotherapeutic drug sensitive group?97patients?and a chemotherapeutic drug resistant group?67 patients?.The proportion of breast cancer tissues expressing LAT1 was positive in 87 cases?53.0%?and negative in 77 cases?47.0%?in the immunohistochemistry experiment.The expression of ATB^0,+was positive for 83 cases?50.6%?and negative for 81 cases?49.4%?.The expression of PTEN was positive in 66 cases?40.2%?and negative in 98 cases?59.8%?.Statistical analysis showed that the expressions of LAT1,ATB^0,+and PTEN were significantly higher in the chemotherapy effective group than that in the chemotherapy resistant group?P=0.016,0.028,0.001?.The expressions of LAT1 and PTEN were positively correlated?P=0.011?.Conclusions:1.LAT1,ATB^0,+were highly expressed in breast cancer tissues and located in the breast cancer cell membrane and cytoplasm.2.The high expression of LAT1 was related to the high expression of PTEN.3.In the neoadjuvant chemotherapeutic drug resistant group of breast cancer patients,LAT1,ATB^0,+and PTEN expressions were all lower than those of patients with good efficacy of chemotherapy.4.Breast cancer amino acid transporters LAT1,ATB^0,+can be used as a prognostic indicator to evaluate the efficacy of neoadjuvant chemotherapy for breast cancer.5.Breast cancer amino acid transporters LAT1 and ATB^0,+may be served as a potential therapeutic targets for chemotherapy for breast cancer.