title: Sprouty1 is a candidate tumor-suppressor gene in medullary thyroid carcinoma.
abstract: Medullary thyroid carcinoma (MTC) is a malignancy derived from the calcitonin-producing C-cells of the thyroid gland. Oncogenic mutations of the Ret proto-oncogene are found in all heritable forms of MTC and roughly one half of the sporadic cases. However, several lines of evidence argue for the existence of additional genetic lesions necessary for the development of MTC. Sprouty (Spry) family of genes is composed of four members in mammals (Spry1-4). Some Spry family members have been proposed as candidate tumor-suppressor genes in a variety of cancerous pathologies. In this work, we show that targeted deletion of Spry1 causes C-cell hyperplasia, a precancerous lesion preceding MTC, in young adult mice. Expression of Spry1 restrains proliferation of the MTC-derived cell line, TT. Finally, we found that the Spry1 promoter is frequently methylated in MTC and that Spry1 expression is consequently decreased. These findings identify Spry1 as a candidate tumor-suppressor gene in MTC.
authors.affiliation: Department of Experimental Medicine, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida, Lleida, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Macià
authors.forename: P
authors.initials: P
authors.lastname: Gallel
authors.forename: M
authors.initials: M
authors.lastname: Vaquero
authors.forename: M
authors.initials: M
authors.lastname: Gou-Fabregas
authors.forename: M
authors.initials: M
authors.lastname: Santacana
authors.forename: A
authors.initials: A
authors.lastname: Maliszewska
authors.forename: M
authors.initials: M
authors.lastname: Robledo
authors.forename: J R
authors.initials: JR
authors.lastname: Gardiner
authors.forename: M A
authors.initials: MA
authors.lastname: Basson
authors.forename: X
authors.initials: X
authors.lastname: Matias-Guiu
authors.forename: M
authors.initials: M
authors.lastname: Encinas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D018278:Carcinoma, Neuroendocrine; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D006965:Hyperplasia; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011230:Precancerous Conditions / Q000473:pathology; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D017384:Sequence Deletion; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; C425468:Spry1 protein, mouse; D051096:Proto-Oncogene Proteins c-ret