The regulation of growth of human submandibular salivary gland adenocarcinoma cells (HSG) by glucocorticoids.

糖皮质激素对人颌下唾液腺腺癌细胞（HSG）生长的调节。

• 批准号: 61570862
• 负责人: HATAKEYAMA Setsuko
• 金额: $ 1.54万
• 依托单位: Iwate Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570862/
• 关键词: Glucocorticoid; Glucocorticoid receptor; Salivary gland tumor; Cell growth; Cellular differentiation; Cell cycle; Flow cytometry; Nude mouse; ヌードマウス; 細胞増殖; 株細胞; 細胞肥大ヌードマウス

1) Glucocorticoids induced the inhibition of cellular proliferation (the dectease of DNA synthesis, the prolongation of doubling time, and the decrease of the rate of colony formation) and morphological change of HSG cells after the treatment for 8-16 hours at concentrations of 0.01-0.1 muM. Scatchard plot analysis using [6,7-^3H]-triamcinolone revealed that the HSG cells had apparent cytosolic glucocorticoid receptors with an equilibrium dissociation constant (Kd value) of 6.5 nM whose number of binding sites was 57.8 fmol/mg protein. 2) Glucocorticoids also showed growth-inhibitory effects such as a suppression of tumor growth, the appearance of duct-like structures, and epithelial membrane antigen (EMA)-immunoreactive cells by histological observation of HSG cells transplanted in nude mice by mediating the specific receptors. 3) Glucocorticoids arrested G0-G1 phase in the cell cycle of HSG cells by blocking the transition of G0-G1 to S phase. The action of G0-G1 arrest was observed only in the medium with serum or supplements (10mug/ml insulin, 10 mug/ml transferrin, and 20 mug/ml monoethanolamine) and was nullified by additive EGF (10 ng/ml). Conditioned medium and supplements (insulin, transferrin, and monoethanolamine) did not suppress G0-G1 arrest-effect of glucocorticoids. The simultaneous additions of glucocorticoid and cycloheximide (which was the blocker of protein synthesis) suppressed the glucocorticoid-induced G0-G1 arrest. These results indicate that glucocorticoids probably induce some growthinhibitory factors for HSG cells which compete with the growthstimulating effect of EGF.

1)0.01~0.1um糖皮质激素作用8~16h后，HSG细胞增殖受到抑制(DNA合成下降，倍增时间延长，集落形成率降低)，细胞形态发生改变。[6，7-~3H]-曲安奈德作图分析表明，HSG细胞有明显的胞浆糖皮质激素受体，其平衡解离常数(Kd值)为6.5 nM，结合位点数为57.8fmol/mg蛋白。2)通过对HSG细胞移植到裸鼠体内的组织学观察，发现糖皮质激素还具有抑制肿瘤生长、出现管状结构和上皮膜抗原(EMA)免疫反应细胞等生长抑制作用。3)糖皮质激素通过阻断细胞周期中G0-G1期向S期的转变，使细胞周期停滞于G0-G1期。只有在含血清或补充剂(10µg/ml胰岛素、10µg/ml转铁蛋白和20µg/ml单乙醇胺)的培养液中才能观察到G0-G1期阻滞的作用，并被EGF(10 ng/ml)所阻断。条件培养液和补充剂(胰岛素、转铁蛋白和单乙醇胺)不能抑制糖皮质激素的G0-G1期停滞效应。同时加入糖皮质激素和放线菌酮(蛋白质合成阻滞剂)可抑制糖皮质激素诱导的G0-G1期停滞。提示糖皮质激素可能诱导HSG细胞产生某些生长抑制因子，与EGF的促生长作用相竞争。

项目成果

Setsuko Hatakeyama: "Inhibition of growth in human neoplastic salivary duct cell line (HSG) with glucocorticoid." Igakuno Ayumi. 137. 1101-1102 (1986)

Setsuko Hatakeyama：“用糖皮质激素抑制人肿瘤性唾液管细胞系 (HSG) 的生长。”

Setsuko Hatakeyama: "Glucocorticoid-induced growth inhibition of human neoplastic salivary duct cell line (HSG)." Acta Pathol Jpn. 37. 587-595 (1987)

Setsuko Hatakeyama：“糖皮质激素诱导的人类肿瘤性唾液腺导管细胞系（HSG）的生长抑制。”

畠山節子 他: 医学のあゆみ. 137. 1101-1102 (1986)

Setsuko Hatakeyama 等人：医学史 137. 1101-1102 (1986)

Riki Kurokawa;Setsuko Hatakeyama,et al.: Biochem Int. 13. 671-679 (1986)

Riki Kurokawa；Settsuko Hatakeyama 等人：Biochem Int。

Setsuko Hatakeyama: "Glucocorticoid-induced Gl arrest of the cell cycle and the release effect of epidermal growth factor in the human salivary gland adenocarcinoma cells." (this paper has been submitted to Cance Research).

Setsuko Hatakeyama：“糖皮质激素诱导的细胞周期 G1 阻滞和人唾液腺腺癌细胞中表皮生长因子的释放作用。”