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新型蛋白质PTPIP51在人类角质形成细胞癌及其周围基质中表达。

The novel protein PTPIP51 is expressed in human keratinocyte carcinomas and their surrounding stroma.

作者信息

Koch P, Stenzinger A, Viard M, Märker D, Mayser P, Nilles M, Schreiner D, Steger K, Wimmer M

机构信息

Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Germany.

出版信息

J Cell Mol Med. 2008 Oct;12(5B):2083-95. doi: 10.1111/j.1582-4934.2008.00198.x.

Abstract

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 beta-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 beta-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 ke

摘要

背景

已知新型蛋白质PTPIP51(SwissProt登录号Q96SD6)在体外可与两种非跨膜蛋白酪氨酸磷酸酶PTP1B和TCPTP相互作用。全长蛋白的过表达可诱导HeLa和HEK293T细胞凋亡(Lv等人,2006年)。PTPIP51表现出组织特异性表达模式,并且在一些哺乳动物组织中,尤其是在人毛囊和毛囊间表皮中,与细胞分化和凋亡相关。PTPIP51蛋白在正常表皮的所有基底层以上各层中表达,而基底层仅含有PTPIP51 mRNA,但缺乏该蛋白。

目的

在转录(mRNA)和翻译(免疫组织化学)水平上,研究PTPIP51在角质形成细胞癌,即人基底细胞癌(BCC)、鳞状细胞癌(SCC)以及鲍温病(BD)和角化棘皮瘤(KA)中的表达。

方法

分别对BCC、SCC、KA和BD的福尔马林固定、石蜡包埋切片进行逆转录聚合酶链反应(RT-PCR)、免疫组织化学及随后的荧光显微镜分析。通过苏木精和伊红(H&E)染色,根据特定形态学特征识别肿瘤及周围基质中的PTPIP51阳性细胞。为了获取有关PTPIP51假定功能的更多信息,分别通过原位末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)法和Ki67/MIB-1抗原染色,研究PTPIP51与凋亡细胞的可能关联以及与增殖细胞的假定负相关。对PTPIP关于以下抗原进行共免疫染色:TCPTP、PTP1B和β-连环蛋白。

结果

在皮肤的BCC和SCC以及KA和BD中检测到PTPIP51表达。两种类型的角质形成细胞癌均显示PTPIP51在恶性角质形成细胞中有特定的定位模式。BCC的PTPIP51阳性细胞形成两种具有不同蛋白亚细胞定位的簇类型,即细胞质和细胞核或主要为膜性,而SCC的研究显示PTPIP51阳性恶性角质形成细胞呈网状外观,主要由膜性定位形成。BD和KA类似于SCC中PTPIP51表达的结果。此外,我们观察到BCC中PTP1B和PTPIP51部分共定位。SCC和BCC显示PTPIP51与β-连环蛋白共表达且部分共定位。发现一些PTPIP51阳性细胞发生凋亡。PTPIP51也在构成周围基质微环境的细胞中表达。这在肿瘤周围血管内衬的内皮细胞以及先天和适应性免疫系统的浸润细胞中尤为明显。

结论

结果显示PTPIP51在BCC和SCC中主要呈明显的膜性表达模式。由于在肿瘤周围组织中也检测到PTPIP51,该蛋白可能在……中起关键作用

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdf3/4506173/a35a9824bf8b/jcmm0012-2083-f1.jpg

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