Expression of Jun activation domain-binding protein 1 and p27 (Kip1) in thyroid medullary carcinoma.
OBJECTIVE
p27 is a prominent regulator of cell proliferation by universally inhibiting the cell cycle, while Jun activation domain-binding protein 1 (Jab1), a multifunctional cell signaling protein, contributes to carcinoma progression by degrading p27. In this study, we investigated the expression of these proteins in medullary thyroid carcinoma.


METHODS
We immunohistochemically examined Jab1 and p27 expression in 64 medullary thyroid carcinomas.


RESULTS
Of the 64 cases examined, decreased p27 expression was observed in 38 cases (59.4%). The p27 expression level was inversely linked to tumour size as well as plasma calcitonin level. Jab1 expression level was generally high, and 46 cases (71.9%) were classified as overexpressing Jab1. The incidence was higher than those in papillary and follicular carcinomas, which were previously reported. Jab1 expression level was inversely linked to that of p27, and all five cases with only cytoplasmic but not nuclear staining of p27 overexpressed Jab1.


CONCLUSIONS
These findings suggest that (1) decrease in p27 expression may contribute to local tumour growth; (2) Jab1 expression is related to the progression of medullary carcinoma by decreasing the amount of p27 in the cell and accelerating its degradation; and (3) Jab1 may play a more vital role in the pathogenesis of medullary carcinoma than papillary and follicular carcinomas.
Ito
Yasuhiro
Y
Department of Surgery, Kuma Hospital, 8-2-35, Shimoyamate-dori, Chuo-ku, Kobe, Japan. ito01@kuma-h.or.jp
Yoshida
Hiroshi
H
Nakamura
Yasushi
Y
Tomoda
Chisato
C
Uruno
Takashi
T
Takamura
Yuuki
Y
Miya
Akihiro
A
Kobayashi
Kaoru
K
Matsuzuka
Fumio
F
Kuma
Kanji
K
Kakudo
Kennichi
K
Miyauchi
Akira
A
D000328:Adult; D000075686:COP9 Signalosome Complex; D018276:Carcinoma, Medullary / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000096:biosynthesis*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; C413374:p27 antigen; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex