VILIP-1 expression in vivo results in decreased mouse skin keratinocyte proliferation and tumor development.
VILIP-1 expression in vivo results in decreased mouse skin keratinocyte proliferation and tumor development.
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DOI：
10.1371/journal.pone.0010196
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发表时间：
2010-04-15
期刊：
影响因子：
3.7
通讯作者：
Klein-Szanto AJ
中科院分区：
文献类型：
--
作者：
Fu J;Jin F;Zhang J;Fong K;Bassi DE;Lopez De Cicco R;Ramaraju D;Braunewell KH;Conti C;Benavides F;Klein-Szanto AJ
VILIP-1是神经元Ca 2+传感器蛋白家族的成员，能够通过抑制细胞增殖和迁移而在癌细胞中充当肿瘤抑制剂。为了研究VILIP-1在皮肤癌发生中的作用，我们产生了在牛角蛋白K5启动子（K5-VILIP-1）的控制下在表皮中过表达VILIP-1的转基因小鼠。我们研究了FVB野生型和VILIP-1转基因小鼠对化学介导的致癌作用的易感性。在用两阶段致癌方案治疗30周后，所有动物均显示出大量皮肤肿瘤。然而，相对于在野生型（WT）小鼠中观察到的相应的鳞状细胞癌（SCC）多样性，K5-VILIP-1小鼠显示出降低了约49%（p<0.02）的SCC多样性。此外，与WT小鼠中的SCC相比，K5-VILIP 1小鼠中I级低级皮肤SCC（根据Broders分级量表由分化模式定义）的相对百分比增加约50%。使用苯并（a）芘（B（a）P）的皮肤致癌作用的完整致癌方案观察到类似的趋势。对肿瘤和原代表皮角质形成细胞培养物的进一步研究表明，与野生型小鼠相比，K5-VILIP-1小鼠的基质金属蛋白酶9（MMP-9）水平和细胞增殖降低。此外，K5-VILIP-1角质形成细胞中的金属蛋白酶组织抑制剂1（TIMP-1）表达更高。这些结果表明，VILIP-1过表达降低了实验小鼠癌症模型中皮肤癌发生的易感性，从而支持其作为肿瘤抑制基因的作用。
VILIP-1, a member of the neuronal Ca2+ sensor protein family, is able to act as a tumor suppressor in carcinoma cells by inhibiting cell proliferation and migration. In order to study the role of VILIP-1 in skin carcinogenesis we generated transgenic mice overexpressing VILIP-1 in epidermis under the control of the bovine keratin K5 promoter (K5-VILIP-1). We studied the susceptibility of FVB wild type and VILIP-1 transgenic mice to chemically mediated carcinogenesis. After 30 weeks of treatment with a two-stage carcinogenesis protocol, all animals showed numerous skin tumors. Nevertheless, K5-VILIP-1 mice showed decreased squamous cell carcinoma (SCC) multiplicity of ∼49% (p<0.02) with respect to the corresponding SCC multiplicity observed in wild type (WT) mice. In addition, the relative percentage of low-grade cutaneous SCCs grade I (defined by the differentiation pattern according to the Broders grading scale) increased approximately 50% in the K5-VILIP1 mice when compared with SCCs in WT mice. Similar tendency was observed using a complete carcinogenesis protocol for skin carcinogenesis using benzo(a)pyrene (B(a)P). Further studies of tumors and primary epidermal keratinocyte cultures showed that matrix metalloproteinase 9 (MMP-9) levels and cell proliferation decreased in K5-VILIP-1 mice when compared with their wild counterparts. In addition tissue inhibitor of metalloproteinase 1 (TIMP-1) expression was higher in K5-VILIP-1 keratinocytes. These results show that VILIP-1 overexpression decreases the susceptibility to skin carcinogenesis in experimental mouse cancer models, thus supporting its role as a tumor suppressor gene.
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影响因子：
3.6
作者：
Papp, H;Czifra, G;Bíró, T
通讯作者：
Bíró, T
影响因子：
11.2
作者：
Bassi, DE;De Cicco, RL;Klein-Szanto, AJP
通讯作者：
Klein-Szanto, AJP
DOI：
10.1007/s100060050069
发表时间：
1998-09-01
期刊：
Mund-, Kiefer- und Gesichtschirurgie : MKG
影响因子：
--
作者：
Junghanel, A;Berndt, A;Hyckel, P
通讯作者：
Hyckel, P
影响因子：
4.7
作者：
KLEINSZANTO, AJP;NETTESHEIM, P;OLSON, AC
通讯作者：
OLSON, AC
DOI：
10.1073/pnas.90.3.1013
发表时间：
1993-02-01
影响因子：
11.1
作者：
RUGGERI, B;DIRADO, M;KLEINSZANTO, AJP
通讯作者：
KLEINSZANTO, AJP