Background:The expression of Ltype amino-acid transporter 1 (LAT1) is tumour-specific and has been shown to have essential roles in cell growth and survival. However, little is known regarding the clinical significance of LAT1 expression in pancreatic cancer. This study was conducted to determine the prognostic significance of LAT1 expression.Methods:A total of 97 consecutive patients with surgically resected pathological stage I–IV pancreatic ductal adenocarcinoma were retrospectively reviewed. Tumour sections were stained by immunohistochemistry for LAT1, CD98, Ki-67 and vascular endothelial growth factor (VEGF), and microvessel density was determined by CD34 and p53.Results:L-type amino-acid transporter 1 and CD98 were highly expressed in 52.6% (51/97) and 56.7% (55/97) of cases, respectively (P=0.568). The expression of LAT1 within pancreatic cancer cells was significantly associated with disease stage, tumour size, Ki-67, VEGF, CD34, p53 and CD98. Ltype amino-acid transporter 1 expression was confirmed to be a significant prognostic factor for predicting poor outcome by multivariate analysis.Conclusion:Ltype amino-acid transporter 1 expression is a promising pathological marker for the prediction of outcome in patients with pancreatic cancer.

Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98) (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC. (Cancer Sci 2012; 103: 382-389) B reast cancer is a heterogeneous disease, and for many years invasive breast cancer was classified according to the extent of tumor spread, histological features and expression of the hormonal receptors, estrogen receptor (ER) and progesterone receptor (PgR). The subtypes that express hormonal receptors have been predicted to respond to endocrine therapy with tamoxifen (1) or aromatase inhibitors for two decades.(2) Recently, human epidermal growth factor receptor-2 (HER2) expression status has attracted a great deal of attention, because anti-HER2 therapies, such as trastuzumab treatment, have improved patient prognosis.(3-5) However, there are no targeted therapeutic agents for triple negative breast cancer (TNBC) (which is negative for ER, PgR and HER2) because of its heterogeneity, and the only treatment option is conventional systemic chemotherapy, despite its aggressive behavior.(6-12) Basal-like phenotype, which is classified by gene expression and low levels of ER, an absence of HER2 overexpression and positive basal-marker expression, clinically overlaps with TNBC.(12) Mutations in BRCA1 are reported to confer a high risk of development of the basal-like subtype, and loss of BRCA1 function is one of the determinants for the treatment of this phenotype. CD98 (4F2hc) was discovered through screening of mRNA to identify membrane pro...

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The effects of natriuretic peptides on the proliferation and differentiation of osteoblast-like cells from rat calvariae were examined. Natriuretic peptides are physiological agonists that activate receptor guanylate cyclases, namely, natriuretic peptide receptor (NPR)-A and NPR-B. Exposure of cells to atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) resulted in large increases in the rate of intracellular production of guanosine 3',5'-cyclic monophosphate (cGMP). Moreover, CNP-like immunoreactivity was detected in the conditioned medium from osteoblast-like cells, while ANP was undetectable. In cells exposed to natriuretic peptides, a dose-dependent reduction in the rate of DNA synthesis was observed. Natriuretic peptides also stimulated the activity of alkaline phosphatase (ALPase) and the expression of mRNA for ALPase and osteocalcin and the mineralization of nodules by the cultured cells. These results could be reproduced by treating cells with 8-bromo-cGMP. Endothelin-1, whose physiological functions are the opposite of those of natriuretic peptides, decreased the ALPase activity and the mineralization of nodules. In the present study, natriuretic peptides were demonstrated to promote bone formation via the action of cGMP in a signal-transduction pathway mediated by specific receptors in osteoblast-like cells.