ABSTRACT
BACKGROUND: The incidence of basal cell carcinoma (BCC) is increasing and the costs for care rising. Therefore, the need for simplified and cost-effective treatment choices is substantial. Aberrant signalling in several pathways, induced by ultraviolet radiation, is of importance in the development of BCC. Alterations in tumour metabolic activity are part of general carcinogenesis; however, these alterations are only partially recognized in skin cancer. OBJECTIVES: To study expression profiles in BCCs compared with individually matched nontumour skin, with a focus on finding differences associated with tumour metabolism. MATERIALS AND METHODS: Gene expression in biopsies from BCCs (n = 14) compared with biopsies from nontumour gluteal skin was analysed with microarrays (n = 4 + 4) and/or quantitative real-time polymerase chain reaction (qPCR, n = 14 + 14). Protein expression and localization was assessed using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded BCC samples. RESULTS: Microarray analysis revealed increased expression of the amino acid transporters SLC7A5, SLC7A7 and SLC7A8 as well as the cytosolic enzyme tryptophan 2,3-dioxygenase (TDO) 2 in BCC. Higher expression of SLC7A5 (P < 0·001), SLC7A8 (P < 0·001) and TDO2 (P = 0·002), but not SLC7A7 (P = 0·50), was confirmed by qPCR, and IHC demonstrated correlating tumour cell protein expression of SLC7A5 and SLC7A8. Protein expression of SLC7A7 was observed in the stratum granulosum, and TDO2 in immune cells. CONCLUSIONS: 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.
Subject(s)
Carcinoma, Basal Cell/pathology , Skin Neoplasms/pathology , Aged , Aged, 80 and over , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+L , Cohort Studies , Female , Fusion Regulatory Protein 1, Light Chains/metabolism , Humans , Large Neutral Amino Acid-Transporter 1/metabolism , Male , Middle Aged , Skin/pathology , Tryptophan Oxygenase/metabolism , Up-RegulationABSTRACT
A new proline-rich polypeptide (PRP-1) has been earlier shown to possess a broad spectrum of biological activities and seems to be a potential medicine. The potential genotoxic properties of PRP-1 and protective effect of PRP-1 against genotoxic action of Mitomycin C (MMC) were analyzed in details in the present work. DNA and chromosome damages were studied in KCL-22 cell line of human myeloid leukemia by the Comet assay and micronucleus induction test, respectively. The results suggest that DNA damages are, at least partly, transient and reparable. PRP-1 at the doses 0.5-2.0 microg/ml does not possess genotoxic activity. Moreover, this peptide expresses both preventive and therapeutic effects against MMC-induced DNA damage. Pre-treatment of cells with PRP-1 also prevents the appearance of daughter cells bearing as heavy MMC-induced DNA/chromosome damages as MNs. Thus, the polypeptide studied is able to protect the cells from genotoxic action of MMC. This defense includes not only DNA but also heritable chromosome damage in post-mitotic cells. Possible mechanisms of PRP-1 protective action are discussed.
