Expression Of TGFβ Receptor-activated Smads And Common-partner Smad In Seborrheic Keratosis, Basal Cell Carcinoma And Squamous Cell Carcinoma

Background:Smads are important intracellular mediators and regulators in the intracellular signal transduction pathway of transforming growth factorβ(TGFβ).The intracellular signaling of TGFβfrom the membrane receptors to nucleus is mediated and regulated by some Smad proteins.Among these Smads,TGFβreceptor-activated Smads such as Smad2 and Smad3,and common-partner Smad----Smad4 are the key molecules in TGFβsignaling pathway.The blockade of TGFβ/Smad signaling pathway is involved in photoaging,ultraviolet radiation and tumorigenesis in epithelial tumors.Seborrheic keratosis,basal cell carcinoma and squamous cell carcinoma are clinically common epidermal tumors associated with skin aging and ultraviolet radiation.In our previous studies,we found that the down-regulated expressions of TGFβreceptorⅠandⅡ(TGF-βRⅠandⅡ) and up-regulated expressions of Smad ubiquitination regulatory factor 1 and 2(Smurf1 and Smurf2) and Smad7 in seborrheic keratosis,basal cell carcinoma and squamous cell carcinoma.Based on the experimental findings that Smurf and Smad7 interfere with multiple steps of TGFβ/Smads signaling pathway,we suppose that more aberrant changes exist in TGFβ/Smad signaling pathway.Whether the expression levels of TGFβreceptor-activated Smad,such as Smad2/3 and common-partner Smad----Smad4 are changed in seborrheic keratosis,basal cell carcinoma and squamous cell carcinoma remain unknown.Objective:To investigate the expressions of TGFβreceptor-activated Smads and common-partner Smad in seborrheic keratosis,basal cell carcinoma and squamous cell carcinoma,for an insight into the correlation between aberrant TGFβsignaling and tumorous hyperplasia in the epidermal tumors mentioned above.Method:Reverse transcription(RT) and quantitative real-time polymerase chain reaction(real-time PCR) technique was utilized to assess the expresions of Smad2,Smad3 and Smad4 mRNA in seborrheic keratosis,basal cell carcinoma,squamous cell carcinoma and normal control skin.The expresions of Smad1/2/3,p-Smad2/3 and Smad4 proteins in seborrheic keratosis,basal cell carcinoma,squamous cell carcinoma and normal control skin were detected using EliVision^TM plus immunohistochemical technique.Results:RT and real-time PCR revealed that the expression levels of Smad2,Smad3 and Smad4 mRNA in seborrheic keratosis,basal cell carcinoma and squamous cell carcinoma were markedly down-regulated in comparison with those of normal control skin. Immunohistochemistry also showed that the expressions of Smadl/2/3,pSmad2/3 and Smad4 protein were significantly decreased in comparison with those of normal control skin.Conclusion:The down-regulated expression of TGFβreceptor-activated Smads and common-partner Smad existed in seborrheic keratosis,basal cell carcinoma and squamous cell carcinoma.The decreased expression or absence of these Smads might lead to the blockade of TGFβsignaling.Under the integrated action of activated oncogene,inactivated tumor suppressor gene and other related regulatory factors,keratinocytes and epithelial tumor cells without inhibition of TGFβon cell proliferation might develop the pathological change of aberrant hyperplasia in the epidermal tumors like seborrheic keratosis,basal cell carcinoma and squamous cell carcinoma.