Abstract
Stomatin-like protein 2 (SLP-2) is a novel and unusual stomatin homologue of unknown functions. It has been implicated in interaction with erythrocyte cytoskeleton and presumably other integral membrane proteins, but not directly with the membrane bilayer. We show here the involvement of SLP-2 in human esophageal squamous cell carcinoma (ESCC), lung cancer, laryngeal cancer, and endometrial adenocarcinoma and the effects of SLP-2 on ESCC cells. Previous work of cDNA microarray in our laboratory revealed that SLP-2 was significantly up-regulated in ESCC. The expression of SLP-2 was further evaluated in human ESCC, lung cancer, laryngeal cancer, and endometrial adenocarcinoma by semiquantitative reverse transcription-PCR, Western blot, and immunohistochemistry. Mutation detection of SLP-2 exons was done by PCR and automated sequencing. Antisense SLP-2 eukaryotic expression plasmids were constructed and transfected into human ESCC cell line KYSE450. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, clonogenecity assay, flow cytometry assay, nude mice tumorigenetic assay, and cell attachment assay were done to investigate the roles of SLP-2 gene. All tumor types we tested showed overexpression of SLP-2 compared with their normal counterparts (P < or = 0.05). Moreover, immunohistochemistry analysis of mild dysplasia, severe dysplasia, and ESCC showed that overexpression of SLP-2 occurred in premalignant lesions. Mutation analysis indicated that no mutation was found in SLP-2 exons. KYSE450 cells transfected with antisense SLP-2 showed decreased cell growth, proliferation, tumorigenecity, and cell adhesion. SLP-2 was first identified as a novel cancer-related gene overexpressed in human ESCC, lung cancer, laryngeal cancer, and endometrial adenocarcinoma. Decreased cell growth, cell adhesion, and tumorigenesis in the antisense transfectants revealed that SLP-2 may be important in tumorigenesis.
Highlights
Esophageal squamous cell carcinoma (ESCC), the major histologic form of esophageal cancer, is one of the most frequent fatal malignancies in the world, especially in the northern part of China
Previous work on cDNA microarry representing 34,176 clones revealed that Stomatin-like protein 2 (SLP-2) was up-regulated over six times in ESCC tissues [11, 12]
Previous work on cDNA microarry and RT-PCR revealed that SLP-2 was up-regulated over six times in ESCC [8, 11, 12]
Summary
Esophageal squamous cell carcinoma (ESCC), the major histologic form of esophageal cancer, is one of the most frequent fatal malignancies in the world, especially in the northern part of China. Human ESCC carcinogenesis is a Authors’ Affiliations: 1National Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College ; 2MOE Key Laboratory of Bioinformatics, Department of Automation, Tsinghua University, Beijing, P.R. China; and 3Department of Thoracic Surgery, the First Affiliate Hospital of Anhui Medical University, Hefei, P.R. China Received 8/24/05; revised 12/4/05; accepted 12/27/05. SLP-3 is expressed in olfactory sensory neurons [13, 16] All of these proteins as well as the stomatin from other species share a characteristic NH2-terminal hydrophobic domain as well as a consensus stomatin signature sequence that defines the stomatin gene family [13]. Similar to other family members, SLP-2 shares the cognate stomatin signature sequence. It is the first member of this family to be recognized that lacks an NH2-terminal hydrophobic domain [13]. The identification of SLP-2 as a novel cancer-related gene may have implications for understanding tumorigenesis
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