Involvement of PTEN/Akt signaling in capsular invasive carcinomas developed in a rat two-stage thyroid carcinogenesis model after promotion with sulfadimethoxine.
OBJECTIVE
Rat thyroid follicular cell carcinomas invading into the thyroid capsule are highly produced by promotion with sulfadimethoxine (SDM) in a rat two-stage thyroid carcinogenesis model. In this study, we investigated the participation of phosphoinositide 3-kinase (PI3K) signaling pathway that is associated with malignant phenotypes of many cancers on the development of SDM-induced capsular invasive carcinomas.


METHODS
Thyroid proliferative lesions developed 10 or 15 weeks after promotion with SDM in male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine were immunohistochemically analyzed with regard to cellular distribution of phosphatase and tensin homolog (PTEN) and Akt isoforms, as well as their downstream molecules.


RESULTS
Increased expression of PI3K signaling molecules was evident in association with the development of lesion stages from the early focal hyperplasia to the late carcinomas. Capsular carcinomas, and the less frequent parenchymal carcinomas, exclusively expressed phosphorylated, inactive PTEN, and active Akt isoforms, as did their downstream molecules. Among the Akt isoforms, enhanced expression of Akt1 was more prominent than that of Akt2 in both capsular and parenchymal carcinomas.


CONCLUSIONS
Activation of the PI3K pathway through phosphorylation of PTEN promotes the high production of capsular carcinomas as well as the development of less frequent parenchymal carcinomas.
Kemmochi
Sayaka
S
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
Fujimoto
Hitoshi
H
Woo
Gye-Hyeong
GH
Inoue
Kaoru
K
Takahashi
Miwa
M
Mitsumori
Kunitoshi
K
Hirose
Masao
M
Nishikawa
Akiyoshi
A
Shibutani
Makoto
M
D000818:Animals; D049109:Cell Proliferation; D007150:Immunohistochemistry; D008297:Male; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects*; D013412:Sulfadimethoxine / Q000633:toxicity*; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000473:pathology
D013412:Sulfadimethoxine; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat