The Expression And Significance Of LXRβ In Cutaneous Squamous Cell Carcinoma

Background:Cutaneous squamous cell carcinoma(cSCC)is malignancy derived from cutaneous keratocytic cells of epidermis and which is classified as non-melanoma skin cancer,NMSC.Cutaneous squamous cell carcinoma is the second common type skin cancer,whose mortality is lower than that of the basal cell carcinoma only.Squamous cell carcinoma occurs on the head,neck and other naked sites.The patients at early stage sometimes pay less attention to the skin lesion,until the lesions turn to be larger,deeper infiltrated,or even distant metastasizing.So the prognosis of c SCC is poor.With more evidence emerged,many studies show that some metabolism related genes have abnormal expression in a variety of tumor cells,which have closely connection to the tumorigenesis,progression and metabolism of tumor.Liver X receptor(LXRs),which acts as a lipid synthesis and metabolism of the key regulatory factors,and its downstream genes can regulate and control the proliferation and apoptosis of tumor through affecting the tumor microenvironment.In preliminary study,we found that LXRs have different expression in human keratinocytes and skin squamous cell carcinoma cell line,and the expression of LXRβ was significantly higher than that of LXRα in both cell lines.However,whether the different expression of LXRs is related to the occurrence and development of skin squamous cell carcinoma,there has no relevant reported.In this study,we detected the expression of m RNA and protein in skin normal keratinocytes(KC)and skin squamous cell carcinoma cell line A431,and analyzed the trends of LXRβ in the progression of cSCC disease.By analyzing correlation between LXRβ and clinicopathological parameters of cSCC,we explore the role of LXR in the development and progression of skin squamous cell carcinoma.Objective :To observe the expression of LXRs in keratinocytes and skin squamous cell carcinoma cell line A431.To observe the expression and distribution of LXRβ in normal skin(NS),actinic keratosis(AK),Bowen’s disease(BD)and c SCC.The analysis of relationship between the expression of LXRβ and the clinical parameters of patients is aimed at deepening the understanding of the mechanism of LXRβ in the progression of skin squamous cell carcinoma.Methods :1.The LXRs’ m RNA level in KC and A431 was detected by PCR array.2.The protein expression of LXRβ in KC and A431 was measured by western blot.3.Immunohistochemical staining(Envision method)was used to reveal the expression pattern of LXRβ in c SCC and correlated precancerous lesions.The expression of LXRβ in the tissues of normal skins(n=40),AKs(n=52),BDs(n=40)and cSCCs(n=60)were detected.Results:1.Compared with KC,the mRNA level of LXRβ in A431 cells is much higher.2.Compared with KC,the protein level of LXRβ in A431 cells is much higher.LXRβ is the dominant expression subtype.3.Immunohistochemical staining shows that the expression of LXRβ in cSCC tissue is increasing gradually from normal tissue to cancer.Conclusion:1.LXRs were differentially expressed in KC cells and A431 cells,and LXRβ has the dominant expression.2.LXRβ in squamous cell carcinoma A431 cells and tissues was over-expressed.The expression of LXRβ in normal skin,actinic keratosis,Bowen’s disease and skin squamous cell carcinoma increased gradually,suggesting that LXRβ is involved in tumor proliferation and differentiation during the development and progression of cutaneous squamous cell carcinoma.3.In different stages of squamous cell carcinoma,the expression of LXRβ in BD,well and moderately differentiated squamous cell carcinoma is higher than that in poorly differentiated c SCC.We speculate that LXRs may play role in the initial stage of squamous cell carcinoma.