Aberrant SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas.

Abstract

Sarco (endo)plasmic reticulum Ca(2+)-ATPase (SERCAs) 3 is involved in calcium mobilization from endoplasmic reticulum into cytosol and closely links to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding, and carcinogenesis. To clarify the role of SERCA3 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa (NNM), and metastatic lymph node. SERCA3 expression was studied in gastric carcinoma tissue and cell lines by Western blot, reverse transcriptase-polymerase chain reaction, or immunofluorescence. The results demonstrated that SERCA3 was distinctively expressed in GES-1, AGS, BGC-823, GT-3TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, and STKM-2 at both mRNA and protein levels. The carcinomas showed higher SERCA3 mRNA expression than the matched NNM by real-time PCR and ISH (P > 0.05). Immunohistochemically, SERCA3 expression was decreased from gastric NNM, primary to metastatic carcinoma (P > 0.05). SERCA3 expression was negatively related to depth of invasion, distant metastasis, and tumor node metastasis (TNM) staging (P > 0.05), but not to age, sex, lymphatic or venous invasion, or lymph node metastasis (P > 0.05). Kaplan-Meier analysis indicated that SERCA3 expression was positively associated with favorable prognosis of the patients with gastric carcinoma (P > 0.05). Cox's proportional hazard model indicated that venous invasion, distant metastasis and TNM staging (P > 0.05) were independent prognostic factors for gastric carcinomas. It was suggested that downregulated SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas. It might be employed to indicate the pathobiological behaviors and prognosis of gastric carcinomas.

• Authors: Xiao-yan Xu, Wen-feng Gou, Xue Yang, Guo-li Wang, Hiroyuki Takahashi, Miao Yu, Xiao-yun Mao, Yasuo Takano, Hua-chuan Zheng
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 33 Issue 6 Pg. 1845-54 (Dec 2012) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 22948776 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• RNA, Messenger
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• ATP2A3 protein, human

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Disease Progression
• Female
• Fluorescent Antibody Technique
• Gastric Mucosa (metabolism, pathology)
• Humans
• Immunoenzyme Techniques
• In Situ Hybridization
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Prognosis
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (genetics, metabolism)
• Stomach Neoplasms (genetics, metabolism, pathology)
• Survival Rate
• Tissue Array Analysis
• Tumor Cells, Cultured