The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis.
The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis.
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DOI：
10.1002/mc.20498
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发表时间：
2009-07
影响因子：
4.6
通讯作者：
Yuspa, Stuart H.
中科院分区：
文献类型：
--
作者：
Virador, Victoria M.;Flores-Obando, Rafael E.;Berry, Adam;Patel, Rinal;Zakhari, Julia;Lo, Yu-Chien;Strain, Kathryn;Anders, Joanna;Cataisson, Christophe;Hansen, Laura A.;Yuspa, Stuart H.
PMLRARα融合显性-负性癌基因在转基因小鼠表皮中的表达导致了自发性皮肤肿瘤，这归因于PML和RAR通路的改变。为了确定PML在皮肤肿瘤易感性中的作用，在FVB/N背景下建立了转基因小鼠，在牛角蛋白5启动子的控制下，人PML蛋白在表皮和毛囊中过表达。PML在这些小鼠的表皮和毛囊中高度表达，在培养的角质形成细胞中也增加，仅限于核体。虽然在年轻转基因小鼠中没有检测到明显的皮肤表型，但角蛋白10(K10)在表皮、毛囊和培养的角质形成细胞中的表达增加。随着年龄的增长，它们表现出广泛的脱发，在C57BL/6J背景下更加突出。以7，12-二甲基苯并[a]菲(DMBA)为引发剂，12-O-十四酰佛波醇-13-乙酸酯(TPA)为启动子诱发皮肤肿瘤后，转基因小鼠中乳头状瘤的多发性和大小降低了35%，并延缓了乳头状瘤向癌的转化。培养的转基因角质形成细胞经历了过早衰老和p16和Rb的转录上调，但没有p19和p53的转录上调。综上所述，这些变化表明PML参与调节角质形成细胞的生长和分化，这可能影响其作为肿瘤发展抑制因子的活性。
Expression of the PMLRARα fusion dominant-negative oncogene in the epidermis of transgenic mice resulted in spontaneous skin tumors attributed to changes in both the PML and RAR pathways. To determine the contribution of PML to skin tumor susceptibility, transgenic mice were generated on an FVB/N background, that overexpressed the human PML protein in epidermis and hair follicles under the control of the bovine keratin 5 promoter. PML was highly expressed in the epidermis and hair follicles of these mice and was also increased in cultured keratinocytes where it was confined to nuclear bodies. While an overt skin phenotype was not detected in young transgenic mice, expression of keratin 10 (K10) was increased in epidermis and hair follicles and cultured keratinocytes. As mice aged, they exhibited extensive alopecia that was accentuated on the C57BL/6J background. Following skin tumor induction with 7, 12-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter, papilloma multiplicity and size were decreased in the transgenic mice by 35%, and the conversion of papillomas to carcinomas was delayed. Cultured transgenic keratinocytes underwent premature senescence and upregulated transcripts for p16 and Rb but not p19 and p53. Together, these changes suggest that PML participates in regulating the growth and differentiation of keratinocytes that likely influence its activity as a suppressor for tumor development.
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DOI：
10.1084/jem.193.4.521
发表时间：
2001-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rego EM;Wang ZG;Peruzzi D;He LZ;Cordon-Cardo C;Pandolfi PP
通讯作者：
Pandolfi PP
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
4.7
作者：
Mu, ZM;Le, XF;Chang, KS
通讯作者：
Chang, KS
影响因子：
4.7
作者：
HENNINGS, H;GLICK, AB;YUSPA, SH
通讯作者：
YUSPA, SH
影响因子：
9.7
作者：
Li, Lei;He, Dalin;Nan, Xunyi
通讯作者：
Nan, Xunyi