Analysis of function of protein kinase C isozymes in pigment cells by gene transfection using adenovirus vectors

腺病毒载体基因转染分析色素细胞中蛋白激酶C同工酶的功能

• 批准号: 11670830
• 负责人: OKA Masahiro
• 金额: $ 2.3万
• 依托单位: Kobe 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 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670830/
• 关键词: protein kinase C; adenovirus vector; pyoderma gangrenosum; interleukin-8; melanin; 黒色腫; プロテインキナーゼC; 色素細胞

We constructed recombinant adenovirus vectors for protein kinase C (PKC) isozymes (α, β, δ, ε, ζ), interleukin-8 (IL-8), constitutively active and dominant negative mutants of phosphatidylinositol 3-kinase (PI 3-kinase), and constitutively active mutant of Akt. Using these adenovirus vectors, we got several results as follows.1. PKCα augments TPA-induced activation of phospholipase D in G361 melanoma cells which do not express PKCα.2. IL-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts.3. PI 3-kinase regulates melanogenesis by modulating the expression of tyrosinase, and activation of Akt is sufficient for suppression of melanin production in G361 melanoma cells.4. Elimination of CD4+T cells enhances antitumor effect of locally secreted interleukin-12 on B16 mouse melanoma and induces vitiligo-likecoat color alteration.

我们构建了蛋白激酶C（PKC）同工酶（α、β、δ、ε、β）、白细胞介素8（IL 8）、磷脂酰肌醇3-激酶（PI 3-kinase）组成型活性突变体和显性失活突变体以及Akt组成型活性突变体的重组腺病毒载体。利用这些腺病毒载体，我们得到了如下结果.在不表达PKCα的G361黑色素瘤细胞中，PKCα增强TPA诱导的磷脂酶D活化。IL-8过表达存在于坏疽性脓疡中，并导致人类皮肤异种移植物中的溃疡形成。PI 3-激酶通过调节酪氨酸酶的表达来调节黑素生成，Akt的激活足以抑制G361黑色素瘤细胞中黑素的生成.清除CD 4 +T细胞增强局部分泌的IL-12对B16小鼠黑色素瘤的抗肿瘤作用并诱导白癜风样皮肤颜色改变。

项目成果

Nagai,H.: "Elimination of CD4+T cells enhances antitumor effect of locally secreted interleukin-12 on B16 mouse melanoma and induces vitiligo-like coat color alteration."Journal of Investigative Dermatology. 115・6. 1059-1064 (2000)

Nagai, H.：“消除 CD4+T 细胞可增强局部分泌的白细胞介素 12 对 B16 小鼠黑色素瘤的抗肿瘤作用，并诱导白癜风样毛色改变。”《皮肤病学研究杂志》115・6 (2000)。

Araki, K.et al: "Small GTPase Rab3A is associated with melanosomes in melanoma cells."Pigment.Cell Res.. 13. 332-336 (2000)

Araki, K. 等人：“小 GTP 酶 Rab3A 与黑色素瘤细胞中的黑色素体相关。”Pigment.Cell Res.. 13. 332-336 (2000)

Oka,M.: "Regulation of melanogenesis through phosphatidylinositol 3-kinase-Akt pathway in human G361 melanoma cells."Journal of Investigative Dermatology. 115. 699-703 (2000)

Oka,M.：“通过人 G361 黑色素瘤细胞中磷脂酰肌醇 3-激酶-Akt 途径调节黑色素生成。”研究皮肤病学杂志。

Satayamoorthy,K.: "An antisense strategy for inhibition of human melanoma growth targets the growth factor pleiotrophin."Pigment Cell Research. 13・Supplement8. 87-93 (2000)

Satayamoorthy, K.：“抑制人类黑色素瘤生长的反义策略以生长因子多效蛋白为目标。”13·补充87-93 (2000)。

Masahiro Oka: "Neutrophil-induced ulcer formation in human skin xenografts after adenovirus-mediated induction of IL-8"Laboratory Investigation. (in press).

Masahiro Oka：“腺病毒介导的 IL-8 诱导后，中性粒细胞在人皮肤异种移植物中诱导溃疡形成”实验室研究。