title: Phosphorylation and inactivation of Tob contributes to the progression of papillary carcinoma of the thyroid.
abstract: Tob, a member of the Tob/BTG family, is a novel anti-proliferative protein, but it becomes inactive when phosphorylated. In this study, we investigated whether Tob is phosphorylated and inactive in various thyroid neoplasms in order to elucidate how this event plays a role in their progression. Tob phosphorylation was only occasionally seen in normal follicular cells. A high level of Tob phosphorylation was observed in 42.1% of follicular adenoma, 14.3% of follicular carcinoma. In papillary carcinoma, the Tob phosphorylation level was elevated more frequently than that in follicular carcinoma, and 39.7% of specimens were classified in the high group. Tob phosphorylation level in papillary carcinoma was directly linked to tumor size, lymph node metastasis, extrathyroid extension and the presence of poorly differentiated lesion. In anaplastic carcinoma, surprisingly, Tob phosphorylation was not observed in any cases, but the deficiency of Tob expression was also observed in all these cases. These results suggest that (1) Tob phosphorylation contributes to the progression of papillary carcinoma especially in the later phase through cancellation of its anti-proliferative function, and (2) the deficiency of Tob expression is attributable to the lack of Tob phosphorylation in anaplastic carcinoma.
authors.affiliation: Kuma Hospital, Kobe 650-0011, Japan. ito01@kuma-h.or.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Chisato
authors.initials: C
authors.lastname: Tomoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Uruno
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takamura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzuka
authors.forename: Kanji
authors.initials: K
authors.lastname: Kuma
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology*; D010766:Phosphorylation; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins