This study highlights the upregulation of SLC7A5, SLC7A8 and TDO2 in BCC compared with nontumour skin. Our findings imply that amino acid transporters may be further explored as potential targets for future medical treatment.
Summary Background Basal cell carcinoma (BCC) is the most common type of cancer in fair‐skinned individuals worldwide. Altered metabolism is a hallmark of cancer, and a growing body of evidence has shown increased expression of the large neutral amino acid transporter small subunit 1 (LAT1) in several types of cancers, including BCC. However, the mechanisms behind changed LAT1 expression in BCC are largely unknown. Aim To describe the protein expression of LAT1 and its colocalization with LAT2, and to examine LAT1 in association with BCC tumour biology characteristics such as cell proliferation, apoptosis and hypoxia. Methods Immunofluorescence stains were used on formalin‐fixed, paraffin‐embedded tissue samples (n = 14) from excised BCCs, and their protein‐staining patterns were examined. Results There was no correlation between expression of LAT1 and LAT2, and the colocalization was low. Compared with normal epidermis, there was significantly higher expression in BCC tissue of the proliferation markers topoisomerase IIα (P < 0.01) and Ki‐67 (P = 0.01). The fraction of LAT1‐expressing cells in BCC tissue was significantly (P < 0.01) inversely correlated with the fraction of proliferative active tumour cells. Cleaved caspase‐3 was significantly (P = 0.02) increased in tumour areas with high LAT1 expression. Conclusions The present study shows that LAT1 is not usually expressed by proliferating BCC cells. The morphological localization suggests that tumour cells use LAT1 to adapt to environmental changes such as starvation and/or hypoxia. These findings could have implications for future development of LAT1‐inhibitory BCC treatments.
Summary Basal cell carcinoma (BCC) is the most common non‐malignant skin cancer and the number of patients with BCC is increasing worldwide. Despite variations between carcinomas, some tumour‐specific changes can be found across all cases. These changes may include expression of tumour specific factors that could help doctors diagnose a BCC or predict its development, which consequently could lead to the development of new target medicines. In our study, we compared gene expressions in basal cell carcinomas with healthy skin. Gene expression is the process by which specific genes are activated to produce a required protein. Essentially, a cell will express certain genes depending on what the role of the cell will be. The authors of this study used microarray, a method allowing analysis of thousands of genes in one single sample. Among the results they found higher expression of genes involved in transport of amino acids (e.g. SLC7A5, SLC7A7 and SLC7A8) and amino acid metabolism (TDO2) to be of further interest. Tumour cells often depend on altered energy usage and need access to building blocks for growth. When comparing the basal cell carcinomas with healthy skin, the genes SLC7A5, SLC7A8 and TDO2 were significantly upregulated (increased) in the carcinomas. The authors could not prove that there was higher gene expression of SLC7A7. Looking at the cellular origin of the four genes, they found that proteins SLC7A5 and SLC7A8 were expressed by the tumour cells while TDO2 was mainly found in the surrounding tissue and in immune cells. The SLC7A7 protein was located in stratum granulosum, which is a thin layer of cells in the outermost layer of skin called the epidermis. SLC7A7 is not likely involved in carcinogenesis (cancer development). In conclusion, the authors identified several proteins with a potential role in BCC that may be potential targets for special drugs, but further research is needed.
Basal cell carcinoma is the most common type of cancer in fair-skinned individuals, and its incidence is rapidly increasing. The aim of the present study was to investigate the gene and protein expression of the mitochondrial solute carrier family 25 member 43 (SLC25A43) in basal cell carcinoma. SLC25A43 has previously been identified to be genetically altered and associated with cell proliferation in human epidermal growth factor receptor 2-positive breast cancer. However, the knowledge about SLC25A43 is limited, and its role in other cancers is unknown. The SLC25A43 gene and protein expression was analysed in 14 basal cell carcinomas and healthy skin samples from the same individuals by quantitative polymerase chain reaction and immunohistochemistry, respectively. The results demonstrated a significantly lower (≥50%) SLC25A43 gene expression in all carcinomas compared with that in healthy skin. In addition, SLC25A43 protein expression was absent in >90% of all visual fields in the basal cell carcinomas, and the H-score was significantly lower in tumours compared with the adjacent epidermis. These results demonstrate that SLC25A43 expression is altered at the gene and protein levels in basal cell carcinoma. The underlying mechanisms and the clinical relevance of these data must be elucidated in additional experimental and clinical studies.
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