The expression and role of serum response factor in papillary carcinoma of the thyroid.

Serum response factor (SRF) is a transcription factor of the MADS box family. SRF is involved in various cellular processes such as expression of immediate early and tissue-specific genes, cell proliferation, differentiation and apoptosis. The expression of SRF in papillary thyroid carcinoma (PTC) and its role have not been investigated, forming the basis for this study. Surgical specimens of 63 conventional PTCs along with 30 follicular adenoma, 30 adenomatous hyperplasia and 9 anaplastic carcinoma specimens were obtained from the surgical archives. The expression of SRF was determined by the use of immunohistochemical staining. We also investigated the expression level of SRF and an SRF target gene, c-fos in fresh PTC tissues and thyroid cancer cell lines (NPA, FRO and ARO) by Western blot analyses. In addition, we examined the role of SRF in PTC by overexpresion of SRF in the NPA cell line. SRF was mainly expressed in cancer cells, showing a strong nuclear and/or cytoplasmic staining in PTC. SRF was expressed in 50 of 63 cases of papillary carcinoma (79%), 18 of 30 cases of follicular adenoma (60%), 10 of 30 cases of nodular hyperplasia (33%) and 6 of 9 cases of anaplastic carcinoma (67%). The expression level of SRF was significantly up-regulated in PTC (combined staining score of 5.21+/-0.43) and anaplastic carcinoma (5.67+/-1.45) compared to that of follicular adenoma (2.30+/-0.44) (P<0.001), or adenomatous goiter (1.13+/-0.28) (P<0.001). Western blot analyses showed an increased expression of the spliced form of SRF protein and c-Fos protein in PTC as compared to non-tumor thyroid tissues. SRF expression correlated with the tumor size of the PTCs (P<0.05). Overexpression of SRF in papillary carcinoma cells enhanced cell motility and invasiveness. Our results indicate that the altered expression of SRF in papillary carcinoma cells may play an important role in PTC carcinogenesis and progression.