Synthesis of 99mTc-EC-AMT as an imaging probe for amino acid transporter systems in breast cancer

2010 ◽  
Vol 31 (8) ◽  
pp. 699-707 ◽  
Author(s):  
Fan-Lin Kong ◽  
YinHan Zhang ◽  
Mohammad S. Ali ◽  
Chanksok Oh ◽  
Richard Mendez ◽  
...  
2020 ◽  
pp. jclinpath-2020-206457
Author(s):  
Masaaki Ichinoe ◽  
Tetuo Mikami ◽  
Nobuyuki Yanagisawa ◽  
Tsutomu Yoshida ◽  
Kiyomi Hana ◽  
...  

AimsL-type amino acid transporter 1 (LAT1) is a major Na+-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.MethodsLAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.ResultsHigh levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.ConclusionsLAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.


2015 ◽  
Vol 469 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Ellappan Babu ◽  
Yangzom D. Bhutia ◽  
Sabarish Ramachandran ◽  
Jaya P. Gnanaprakasam ◽  
Puttur D. Prasad ◽  
...  

Deletion of the amino acid transporter Slc6a14 in mice suppresses tumour growth in spontaneous models of breast cancer via interference with mammalian target of rapamycin (mTOR) pathway; this indicates an obligatory role for SLC6A14 in breast cancer, highlighting its potential as a therapeutic target.


2021 ◽  
Author(s):  
Sasagu Kurouzmi ◽  
Kyoichi Kaira ◽  
Hiroshi Matsumoto ◽  
Masafumi Kurosumi ◽  
Takehiko Yokobori ◽  
...  

Abstract PURPOSE: L-type amino acid transporter 1 (LAT1), also referred to as SLC7A5, is believed to regulate tumor metabolism and be associated with tumor proliferation. In invasive breast cancer, we clinicopathologically investigated the utility of LAT1 expression. METHODS: LAT1 expression was evaluated via immunohistochemistry analyses in 250 breast cancer patients undergoing long-term follow-up. We assessed the relationship between LAT1 expression and the patients’ outcomes and clinicopathological factors. Breast cancer-specific survival stratified by LAT1 expression was assessed.RESULTS: High LAT1 expression was significantly correlated with estrogen receptor (ER) negativity, progesterone receptor negativity, high histological grade, increased tumor-infiltrating lymphocytes, and programmed death ligand 1 positivity. Among the ER-positive and human epidermal growth factor 2-negative type cases, high LAT1 was an independent indicator of poor outcomes (hazard ratio (HR) = 2.97; 95% confidence interval (CI), 1.16–7.62; p = 0.023). Moreover, high LAT1 expression was an independent poor prognostic factor in luminal B-like breast cancer with aggressive features (HR = 3.39; 95% CI, 1.35–8.52; p = 0.0094).CONCLUSIONS: High LAT1 expression identified a subgroup of invasive breast cancer characterized by aggressive behavior and high tumor immunoreaction. Our findings suggest that LAT1 might be a candidate therapeutic target for breast cancer patients, particularly those with luminal B-like type breast cancer.


2011 ◽  
Vol 103 (2) ◽  
pp. 382-389 ◽  
Author(s):  
Mio Furuya ◽  
Jun Horiguchi ◽  
Hiroki Nakajima ◽  
Yoshikatsu Kanai ◽  
Tetsunari Oyama

2010 ◽  
Vol 45 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Zhongxing Liang ◽  
Heidi T. Cho ◽  
Larry Williams ◽  
Aizhi Zhu ◽  
Ke Liang ◽  
...  

2021 ◽  
Vol 22 (13) ◽  
pp. 6706
Author(s):  
Chelsea Thompson ◽  
M Motiur Rahman ◽  
Soudamani Singh ◽  
Subha Arthur ◽  
Cecilia Sierra-Bakhshi ◽  
...  

Obesity increases the risk of postmenopausal breast cancer (BC). This risk is mediated by obesity-induced changes in the adipose-derived secretome (ADS). The pathogenesis of BC in obesity is stimulated by mTOR hyperactivity. In obesity, leucine might support mTOR hyperactivity. Leucine uptake by BC cells is through L-Type Amino Acid Transporter 1 (LAT1). Our objective was to link obesity-ADS induction of LAT1 to the induction of mTOR signaling. Lean- and obese-ADS were obtained from lean and obese mice, respectively. Breast ADS was obtained from BC patients. Estrogen-receptor-positive BC cells were stimulated with ADS. LAT1 activity was determined by uptake of 3H-leucine. The LAT1/CD98 complex, and mTOR signaling were assayed by Western blot. The LAT1 antagonists, BCH and JPH203, were used to inhibit LAT1. Cell migration and invasion were measured by Transwell assays. The results showed obese-ADS-induced LAT1 activity by increasing transporter affinity for leucine. Consistent with this mechanism, LAT1 and CD98 expression were unchanged. Induction of mTOR by obese-ADS was inhibited by LAT1 antagonists. Breast ADS from patients with BMIs > 30 stimulated BC cell migration and invasiveness. Collectively, our findings show that obese-ADS induction of LAT1 supports mTOR hyperactivity in luminal BC cells.


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