The novel protein PTPIP51 is expressed in human keratinocyte carcinomas and their surrounding stroma.
The novel protein PTPIP51 is expressed in human keratinocyte carcinomas and their surrounding stroma.
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DOI：
10.1111/j.1582-4934.2008.00198.x
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发表时间：
2008-10
影响因子：
5.3
通讯作者：
Wimmer M
中科院分区：
文献类型：
--
作者：
Koch P;Stenzinger A;Viard M;Märker D;Mayser P;Nilles M;Schreiner D;Steger K;Wimmer M
背景资料：已知新型蛋白PTPIP 51（SwissProt登录代码Q96 SD 6）在体外与两种非跨膜蛋白酪氨酸磷酸酶PTP 1B和TCPTP相互作用。全长蛋白的过表达诱导HeLa和HEK 293 T细胞的凋亡（Lv等人，2006）。PTPIP 51在某些哺乳动物组织中表现出组织特异性表达模式，并与细胞分化和凋亡相关，特别是在人毛囊和毛囊间表皮中。PTPIP 51蛋白在正常表皮的所有基底上层中表达，而基底层仅含有PTPIP 51 mRNA但缺乏蛋白。目的：在转录（mRNA）和翻译（免疫组织化学）水平上研究了PTPIP 51在角质形成细胞癌（即人基底细胞癌（BCC）和鳞状细胞癌（SCC）以及Bowen病（BD）和角化棘皮瘤（KA））中的表达。研究方法：福尔马林固定，石蜡包埋切片的BCC，SCC，KA和BD，分别进行了分析，通过RT-PCR，以及免疫组化和随后的荧光显微镜。肿瘤和周围基质的PTPIP 51阳性细胞通过H & E染色基于特定的形态学特征来鉴定。为了获得关于PTPIP 51的推定功能的进一步信息，分别通过原位TUNEL测定和Ki 67/MIB-1抗原染色研究PTPIP 51与凋亡细胞的可能关联以及与增殖细胞的假定负相关性。用PTPIP 51对以下抗原进行共免疫染色：TCPTP、PTP 1B和β-连环蛋白。结果：PTPIP 51在皮肤基底细胞癌和鳞状细胞癌中表达，在皮肤角化样增生和白内障中也有表达。这两种类型的角质形成细胞癌揭示了一个特定的定位模式的PTPIP 51在恶性角质形成细胞。而PTPIP 51阳性细胞的BCC被发现形成两个集群类型与不同的亚细胞定位的蛋白质，即细胞质和核或主要是膜，研究SCC显示了网状外观的PTPIP 51阳性恶性角质形成细胞，主要是由膜定位。BD和KA与SCC中PTPIP 51的表达结果相似。此外，我们观察到PTP 1B和PTPIP 51在BCC中的部分共定位。PTPIP 51与β-catenin在SCC和BCC中存在共表达和部分共定位。发现一些PTPIP 51阳性细胞发生凋亡。PTPIP 51也在包含周围基质微环境的细胞中表达。这对于衬于肿瘤周围血管的内皮细胞以及对于先天性和适应性免疫系统两者的浸润细胞特别注意。结论：PTPIP 51在基底细胞癌和鳞状细胞癌中的表达主要以膜表达为主。由于PTPIP 51也在肿瘤周围组织中检测到，该蛋白可能在角质形成细胞肿瘤发展中起关键作用。
Background: The novel protein PTPIP51 (SwissProt accession code Q96SD6) is known to interact with two non-transmembrane protein-tyrosine phosphatases, PTP1B and TCPTP in vitro. Overexpression of the full-length protein induces apoptosis in HeLa and HEK293T cells (Lv et al. 2006). PTPIP51 shows a tissue-specific expression pattern and is associated with cellular differentiation and apoptosis in some mammalian tissues, especially in human follicular and interfollicular epidermis. PTPIP51 protein is expressed in all suprabasal layers of normal epidermis, whereas the basal layer contains PTPIP51 mRNA only but lacks the protein. Objectives: The expression of PTPIP51 was investigated in keratinocyte carcinomas, that is human basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) as well as Bowen's disease (BD) and keratoacanthomas (KAs) on a transcriptional (mRNA) and translational (immunohistochemical) level. Methods: Formalin-fixed, paraffin-embedded sections of BCCs, SCCs, KAs and BD, respectively, were analysed by RT-PCR, as well as immunohistochemistry and subsequent fluorescence microscopy. PTPIP51-positive cells of the tumour and the surrounding stroma were identified on the basis of specific morphological features by means of H & E staining. To obtain further information about a putative function of PTPIP51, a possible association of PTPIP51 with apoptotic cells, as well as an assumed negative correlation with proliferating cells was investigated by means of an in-situ TUNEL assay and Ki67/MIB-1 antigen staining, respectively. Co-immunostainings with PTPIP51 were performed for the following antigens: TCPTP, PTP1B and β-catenin. Results: PTPIP51-expression was detected in BCCs and SCCs of the skin, as well as in KAs and BD. Both types of keratinocyte carcinoma revealed a specific localization pattern of PTPIP51 in malignant keratinocytes. Whereas PTPIP51 -positive cells of BCC were found to form two cluster types with a different subcellular localization of the protein, i.e. cytoplasmic and nuclear or predominantly membranous, investigation of SCC revealed a meshwork-like appearance of PTPIP51-positive malignant keratinocytes, created by a mainly membranous localization. BD and KA resembled the findings of PTPIP51-expression in SCC. Furthermore, we observed a partial co-localization of PTP1B and PTPIP51 in BCC. SCC and BCC showed a co-expression and partial co-localization of PTPIP51 with β-catenin. Some PTPIP51-positive cells were found to undergo apoptosis. PTPIP51 was also expressed in cells comprising the surrounding stromal microenvironment. This was particularly noticed for endothelial cells lining peritumoural vessels as well as for infiltrating cells of both, the innate and the adaptive immune system. Conclusions: The results showed a distinct mainly membranous expression pattern of PTPIP51 in BCCs and SCCs. Since PTPIP51 was also detected in the peritumoural tissue, the protein may play a crucial role in keratinocyte tumour development.