Abnormalitis of growth signaling pathways in human thyroid cancer cells.

人类甲状腺癌细胞生长信号通路异常。

• 批准号: 11671097
• 负责人: TUSHIMA Toshio
• 金额: $ 2.24万
• 依托单位: Tokyo Woman's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671097/
• 关键词: thyroid cancer; MAPK; Akt; MEK; raf-1; Bad; p70S6K; raf-1; 甲状腺癌; 乳頭癌; 濾胞癌; MAPキナーゼ

Several abnormalities of oncogenes have been reported in human thyroid carcinomas. These abnormailites may be involved in molecular events leading to malignant transformation of thyroid carcinoma cells. However, a consistent or unifying pattern of activation of these protonogenes has not been seen, and there is no evidence that they are directly responsible for tumoregenesis. Clearly, events in addition to the activation of these cellular genes are important to the genesis of thyroid papillary carcinoma MAP kinase (MAPK) cascade (ras, rat-i, MEK and MAPK) and phosphoinositol 3 kinase (PI3K)-regulated kinases (PLB/Akt and p7OS6 kinase; p7OS6K) have been shown to play important roles in controlling cell proliferation. We attempted to determine if these pathways are dysregulated in human thyroid tumors. We found that both MAPK and MEK are overexpressed and constitutively activated compared to adjacent normal thyroid cells in a subset of papillary carcinomas and tollicular carcinomas. Expression of those kinases in follicular adenoma was much lower. Cancer cells also showed higher activities of p7OS6K and Akt. These findings suggest that these abnormalities are involved in uncontrolled growth of thyroid cell prolieration in a subset of thyroid cancers. Furthermore , inhibitors of the signaling pathway may be effective in treatment of thyroid cancer.

人类甲状腺癌已经报道了癌基因的几种异常。这些纵大仪可能参与分子事件，从而导致甲状腺癌细胞的恶性转化。但是，尚未看到这些质子基因的一致或统一激活模式，也没有证据表明它们是直接负责肿瘤发生的。显然，除了激活这些细胞基因之外，事件对于甲状腺乳头状癌的生成很重要。增殖。我们试图确定在人甲状腺肿瘤中这些途径是否失调。我们发现，与相邻的乳头状癌和tollicular癌中相邻的正常甲状腺细胞相比，MAPK和MEK都过表达和组成式激活。这些激酶在卵泡腺瘤中的表达要低得多。癌细胞还显示了P7OS6K和AKT的较高活性。这些发现表明，这些异常与甲状腺癌的一部分中甲状腺细胞延长的不受控制的生长有关。此外，信号通路的抑制剂可能有效治疗甲状腺癌。

项目成果

Ohomori N, Tsushima T, Sekine Y, Sato K, Shibagaki Y, Ijuji S, Takano K: "Gearational thyrotoxicosis with acute Wemicke encephalopathy"Endocrine J. 46. 787-793 (1999)

Ohomori N、Tsushima T、Sekine Y、Sato K、Shibagaki Y、Ijuji S、Takano K：“齿轮性甲状腺毒症伴急性 Wemicke 脑病”Endocrine J. 46. 787-793 (1999)

Miyakawa M, Sato K, Hasegawa M, Nagai A, Sawada T, Tsushima T: "Severe thyrotoxicosis induced by thyroid metastasis ot lung denocarcinoma : a case report and rview of the literature"Thyroid. 11. 883-888 (2001)

Miyakawa M、Sato K、Hasekawa M、Nagai A、Sawada T、Tsushima T：“甲状腺转移或肺腺癌引起的严重甲状腺毒症：病例报告和文献综述”甲状腺。

Isozaki O: "Growth hormone directly inhibits leptin gene expression in visceral fat tissue in fatty Zucker rats"Journal of Endocrinology. 161(3). 511-516 (1999)

Isozaki O：“生长激素直接抑制脂肪 Zucker 大鼠内脏脂肪组织中的瘦素基因表达”内分泌学杂志。

Miyakawa M, et al: "Serum leptin levels and bioelectrical impedance assesment of body composition in patients with Graves disease and hypothyroidism."Endocrine Journal. 46(5). 665-673 (1999)

Miyakawa M 等人：“格雷夫斯病和甲状腺功能减退症患者的血清瘦素水平和身体成分的生物电阻抗评估。”内分泌杂志。

Yamauchi T, Yamauchi N, Sugiyama T, Waki H, Miki H, Tone K, Tsushima T et al.: "Constitutive tyrosine phosphorylation of erbB-2 via Jak2 by autocrine secretion of prolactin in human brast cancer"J Biol Chem. 275. 33937-33944 (2000)

Yamauchi T、Yamauchi N、Sugiyama T、Waki H、Miki H、Tone K、Tsushima T 等人：“人乳腺癌中催乳素自分泌通过 Jak2 实现 erbB-2 的组成型酪氨酸磷酸化”J Biol Chem。