Abstract 1337: The distribution of the phosphorylated Parkin in lung carcinoma
Authors: Hongwei Wang, Songlin Zhang, Catherine Ma, Yuan Zhou
Journal: Cancer Research (2017)

Abstract Parkin, also known as Parkinson Juvenile Disease Protein 2, together with PINK1 and Ubiquitin, form a simple cascade in the clearance of damaged mitochondria. This cascade plays an important role in maintain mitochondral quality controls and is implicated in protesomal degradation of toxic substrates. Recent studies have demonstrated that Parkin to be genetically altered, and aberrantly expressed in a variety of human malignancies including lung, breast and ovarian cancers, these may indicate that Parkin is a tumor suppressor gene whose inactivation may play an important role in tumorgenesis. PINK1-dependent phosphorylation of Parkin(pS65) is a required step in Parkin activation and localization. The aims of this study were to investigate the expression of Parkin and its phophorylated form in various type of lung carcinoma tissues and lung cancer cell lines; the correlation of the protein expression level and the type of the cancer. We choose two forms of the cancer materials. 1) A tissue microarray (TMA) which contains 16 cases of lung carcinoma tissues consisting of 8x adenocarcinoma (AC), 6x squamous cell carcinoma (SCC), and 2x small cell lung carcinoma (SCLC); 2) FFPE slides which contains 9x lung cancer cell lines (A549, H1703, H1975, H2228, H23, H838, HOP62, HOP92, and SKMES1). All the tissues and cells were immunohistostained by Parkin and phospho-Parkin polyclonal antibodies. The reference staining was performed by monoclonal anti-Cytokaratin 7 (CK7) antibodies. From this study, we found Parkin expression level varies from TMA tissues and FFPE cell section which were not correlated with tumor grade. Among the 8 cases of andenocarcinoma, only 3/8 showed marked Parkin expression, 3/8 moderate, and 2/8 mild; for Parkin(pS65), only 1/8 demonstrated marked expression, 2/8 moderate, 2/8 mild, and no staining in 3/8 cases. In SCC cases, 2/6 demonstrated marked Parkin expression, 2/6 moderate, 2/6 mild. The phosphorylated Parkin(pS65) only expressed in 3/6 showed mild expression, not the others. Among 2 cases of SCLC, only one showed marked Parkin expression and less extent of Parkin (pS65), the other sample had no staining. In all FFPE cell sections, the strong expression of Parkin and Parkin (pS65) was found in the lung cancer cell lines. An interesting finding was that Parkin(pS65) strongly presented in cells of mitotic phase in these cell lines except H1703 cell line. All the TMA and FFPE slides were confirmed by CK7 monoclonal antibody staining. In summary, Parkin and its phophorylated Parkin (pS65) were found in adenocarcinoma, squamouse cell carcinoma and small cell lung cancers with differentially expressed levels, the degree of expression level was not correlated with tumor grade in these 16 cases. Phosphorlated Parkin (pS65) was strongly expressed in FFPE cancer cell lines at mitotic phase. It is concluded that the function of Parkin in tumor development and the prognosis remain to be further evaluated; it may provide a potential therapeutic approach for lung cancer. Note: This abstract was not presented at the meeting. Citation Format: Hongwei Wang, Songlin Zhang, Catherine Ma, Yuan Zhou. The distribution of the phosphorylated Parkin in lung carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1337. doi:10.1158/1538-7445.AM2017-1337