갑상선질환에서 Sonic Hedgehog 단백질 발현의 임상적 의의
Sonic Hedgehog Protein Expression in Various Thyroid Tissues and Its Clinical Implication
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Purpose: The Hedgehog (Hh) signaling pathway is important in embryonic development including cell differentiation and proliferation. Recently, activation of this pathway has been implicated in several forms of solid cancers. We investigated sonic hedgehog (Shh) protein expression and its relation to differentiation and clinicopathologic characteristics in thyroid cancer cell lines and tissues.Methods: We used five thyroid cancer cell lines: TPC-1, FTC-133, FTC-236, FTC-238, and XTC-1. We made tissue microarray slides using 80 thyroid surgical specimen: 40 benign and 40 malignant lesions. Immunohistochemical staining was performed using anti-Shh antibody. mRNA expression of NIS, thyroglobulin, and CD97 were evaluated by RT-PCR. Cyclopamine was used as a Shh signal inhibitor. Results: Shh expression was more prominent in TPC-1, FTC-133, and XTC-1 cell lines than the others. Cyclopamine downregulated CD97 and upregulated thyroglobulin mRNA expression, but did not induce mRNA expression of NIS. Thyroid tissues showed varied expression of Shh in both benign and malignant diseases. Shh expression was detected in 38 of 50 (76%) normal, in 18 of 25 (72%) non-neoplastic benign, in nine of 15 (60%) benign tumors, and in 31 of 40 (77%) malignant tumors. Shh over-expression was significantly less frequent in papillary thyroid carcinomas than in normal or benign thyroid tissues. In addition, Shh protein expression did not relate to clinicopathologic characteristics in papillary thyroid carcinomas. Conclusion: Thyroid tissues and cell lines vary in expression of Shh. Cyclopamine can induce redifferentiation in thyroid cancer cell lines. Shh protein expression, however, is unrelated to clinicopathologic characteristics in papillary thyroid carcinomas. (Korean J Endocrine Surg 2011;11:234-241)
Abstract
Purpose: The Hedgehog (Hh) signaling pathway is important in embryonic development including cell differentiation and proliferation. Recently, activation of this pathway has been implicated in several forms of solid cancers. We investigated sonic hedgehog (Shh) protein expression and its relation to differentiation and clinicopathologic characteristics in thyroid cancer cell lines and tissues.Methods: We used five thyroid cancer cell lines: TPC-1, FTC-133, FTC-236, FTC-238, and XTC-1. We made tissue microarray slides using 80 thyroid surgical specimen: 40 benign and 40 malignant lesions. Immunohistochemical staining was performed using anti-Shh antibody. mRNA expression of NIS, thyroglobulin, and CD97 were evaluated by RT-PCR. Cyclopamine was used as a Shh signal inhibitor. Results: Shh expression was more prominent in TPC-1, FTC-133, and XTC-1 cell lines than the others. Cyclopamine downregulated CD97 and upregulated thyroglobulin mRNA expression, but did not induce mRNA expression of NIS. Thyroid tissues showed varied expression of Shh in both benign and malignant diseases. Shh expression was detected in 38 of 50 (76%) normal, in 18 of 25 (72%) non-neoplastic benign, in nine of 15 (60%) benign tumors, and in 31 of 40 (77%) malignant tumors. Shh over-expression was significantly less frequent in papillary thyroid carcinomas than in normal or benign thyroid tissues. In addition, Shh protein expression did not relate to clinicopathologic characteristics in papillary thyroid carcinomas. Conclusion: Thyroid tissues and cell lines vary in expression of Shh. Cyclopamine can induce redifferentiation in thyroid cancer cell lines. Shh protein expression, however, is unrelated to clinicopathologic characteristics in papillary thyroid carcinomas. (Korean J Endocrine Surg 2011;11:234-241)
참고문헌 (28)
- Ingham PW, "Hedgehog signaling in animal development: paradigms and principles", Genes Dev, 15, pp.3059~3087 (2001)
- Xie J, "Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors", Cancer Res, 57, pp.2369~2372 (1997)
- Ma X, "Hedgehog signaling is activated in subsets of esophageal cancers", Int J Cancer, 118, pp.139~148 (2006)
- Fukaya M, "Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer", Gastroenterology, 131, pp.14~29 (2006)
- Qualtrough D, "Hedgehog signalling in colorectal tumour cells: induction of apoptosis with cyclopamine treatment", Int J Cancer, 110, pp.831~837 (2004)
- Thayer SP, "Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis", Nature, 425, pp.851~856 (2003)
- Watkins DN, "Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer", Nature, 422, pp.313~317 (2003)
- Sanchez P, "Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling", Proc Natl Acad Sci USA, 101, pp.12561~12566 (2004)
- Taipale J, "Patched acts catalytically to suppress the activity of Smoothened", Nature, 418, pp.892~897 (2002)
- Park SS, "Cyclopamine inhibits cancer cell proliferation in thyroid cancer cell lines", Korean J Endocrine Surg, 7, pp.1~6 (2007)
- Nelson KK, "Expression of the sonic hedgehog pathway molecules in synchronous follicular adenoma and papillary carcinoma of the thyroid gland in predicting malignancy", Surgery, 148, pp.654~660 (2010)
- Goretzki PE, "Growth regulation of normal thyroids and thyroid tumors in man", Recent Results Cancer Res, 118, pp.48~63 (1990)
- Zielke A, "Establishment of a highly differentiated thyroid cancer cell line of Hürthle cell origin", Thyroid, 8, pp.475~483 (1998)
- Schmutzler C, "Retinoic acid increases sodium", iodide symporter mRNA levels in human thyroid cancer cell lines and suppresses expression of functional symporter in nontransformed FRTL-5 rat thyroid cells, 1997, pp.240, 832~838
- Aust G, "CD97: a dedifferentiation marker in human thyroid carcinomas", Cancer Res, 57, pp.1798~1806 (1997)
- Ringel MD, "Molecular diagnosis of residual and recurrent thyroid cancer by amplification of thyroglobulin messenger ribonucleic acid in peripheral blood", J Clin Endocrinol Metab, 83, pp.4435~4442 (1998)
- Chiang C, "Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function", Nature, 383, pp.407~413 (1996)
- Litingtung Y, "Sonic hedgehog is essential to foregut development", Nat Genet, 20, pp.58~61 (1998)
- Bhardwaj G, "Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation", Nat Immunol, 2, pp.172~180 (2001)
- Berman DM, "Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours", Nature, 425, pp.846~851 (2003)
- Karhadkar SS, "Hedgehog signalling in prostate regeneration, neoplasia and metastasis", Nature, 431, pp.707~712 (2004)
- Fagman H, "Genetic deletion of sonic hedgehog causes hemiagenesis and ectopic development of the thyroid in mouse", Am J Pathol, 164, pp.1865~1872 (2004)
- Jang KT, "Immunohistochemical expression of Sonic hedgehog in intraductal papillary mucinous tumor of the pancreas", Appl Immunohistochem Mol Morphol, 15, pp.294~298 (2007)
- Xuan YH, "Relationship between hedgehog signaling pathway molecules and HPV16 infection in uterine cervical cancers", Zhonghua Bing Li Xue Za Zhi, 38, pp.178~182 (2009)
- Yanai K, "Hedgehog signaling pathway is a possible therapeutic target for gastric cancer", J Surg Oncol, 95, pp.55~62 (2007)
- Kim TJ, "Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer: a retrospective study from the view point of new 2010 anatomic stage", prognostic groups, 2011, pp.104, 472~479
- Feldmann G, "Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers", Cancer Res, 67, pp.2187~2196 (2007)
- Gupta S, "Targeting the Hedgehog pathway in cancer", Ther Adv Med Oncol, 2, pp.237~250 (2010)
