Aberrant SERCA3 expression during the colorectal adenoma-adenocarcinoma sequence

Gou,Wen-Feng; Niu,Zhe-Feng; Zhao,Shuang; Takano,Yasuo; Zheng,Hua-Chuan

doi:10.3892/or.2013.2837

Aberrant SERCA3 expression during the colorectal adenoma-adenocarcinoma sequence

Authors:
- Wen-Feng Gou
- Zhe-Feng Niu
- Shuang Zhao
- Yasuo Takano
- Hua-Chuan Zheng
View Affiliations

Affiliations: Cancer Research Center, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China, Clinical Research Institute, Kanagawa Cancer Center, Yokohama 241-0815, Japan
Published online on: November 7, 2013 https://doi.org/10.3892/or.2013.2837
Pages: 232-240

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 is involved in calcium mobilization from the endoplasmic reticulum into the cytosol and is closely linked to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding and carcinogenesis. In order to elucidate the role of SERCA3 in colorectal carcinogenesis and subsequent progression, its expression was examined using immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing colorectal carcinomas, adjacent non-neoplastic mucosa (NNM) and adenoma, and metastatic carcinoma in lymph node and liver. Colorectal carcinoma tissue and cell lines were assessed for SERCA3 expression by western blotting or RT-PCR, respectively. SERCA3 was distinctively expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620 and WiDr cells at both the mRNA and protein levels. SERCA3 mRNA expression was low in carcinoma when compared to that in matched NNM by quantitative PCR (P<0.05), while the converse was true by ISH. Lower expression of SERCA3 was immunohistochemically observed in colorectal carcinoma when compared to that in NNM and adenoma (P<0.05). In contrast, primary carcinoma showed high SERCA3 expression when compared to that in metastatic carcinoma in lymph node or liver by IHC (P<0.05). Immunohistochemically, SERCA3 expression was negatively related to lymphatic invasion, but not with age, gender, depth of invasion, venous invasion, lymph node metastasis, distant metastasis, TNM stage, degree of differentiation or survival rate (P>0.05). There was a positive relationship between SERCA3 expression and serum CEA levels in the carcinoma patients (P<0.05). Cox's proportional hazards model indicated that depth of invasion and distant metastasis are independent prognostic factors for overall colorectal carcinomas (P<0.05). These findings suggest that aberrant SERCA3 expression is closely linked to the adenoma-adenocarcinoma sequence and progression of colorectal carcinomas.

View Figures

View References

1	Hovnanian A: SERCA pumps and human diseases. Subcell Biochem. 45:337–363. 2007. View Article : Google Scholar
2	Wuytack F, Dode L, Baba-Aissa F, et al: The SERCA3-type of organellar Ca²⁺ pumps. Biosci Rep. 15:299–306. 1995. View Article : Google Scholar : PubMed/NCBI
3	Baba-Aïssa F, Raeymaekers L, Wuytack F, et al: Purkinje neurons express the SERCA3 isoform of the organellar type Ca(2+)-transport ATPase. Brain Res Mol Brain Res. 41:169–174. 1996.PubMed/NCBI
4	Chandrasekera PC, Kargacin ME, Deans JP, et al: Determination of apparent calcium affinity for endogenously expressed human sarco(endo)plasmic reticulum calcium-ATPase isoform SERCA3. Am J Physiol Cell Physiol. 296:C1105–C1114. 2009. View Article : Google Scholar
5	Kao J, Fortner CN, Liu LH, et al: Ablation of the SERCA3 gene alters epithelium-dependent relaxation in mouse tracheal smooth muscle. Am J Physiol Lung Cell Mol Physiol. 277:L264–L270. 1999.PubMed/NCBI
6	Liu LH, Paul RJ, Sutliff RL, et al: Defective endothelium-dependent relaxation of vascular smooth muscle and endothelial cell Ca²⁺ signalling in mice lacking sarco(endo)plasmic reticulum Ca²⁺-ATPase isoform 3. J Biol Chem. 272:30538–30545. 1997. View Article : Google Scholar : PubMed/NCBI
7	Roe MW, Philipson LH, Frangakis CJ, et al: Defective glucose-dependent endoplasmic reticulum Ca²⁺ sequestration in diabetic mouse islets of Langerhans. J Biol Chem. 269:18279–18282. 1994.PubMed/NCBI
8	Varadi A, Lebel L, Hashim Y, et al: Sequence variants of the sarco(endo)plasmic reticulum Ca²⁺-transport ATPase 3 gene (SERCA3) in Caucasian type II diabetic patients (UK Prospective Diabetes Study 48). Diabetologia. 42:1240–1243. 1999.PubMed/NCBI
9	Arredouani A, Guiot Y, Jonas JC, et al: SERCA3 ablation does not impair insulin secretion but suggests distinct roles of different sarcoendoplasmic reticulum Ca²⁺ pumps for Ca²⁺ homeostasis in pancreatic β-cells. Diabetes. 51:3245–3253. 2002. View Article : Google Scholar : PubMed/NCBI
10	Gélébart P, Kovács T, Brouland JP, et al: Expression of endomembrane calcium pumps in colon and gastric cancer cells. Induction of SERCA3 expression during differentiation. J Biol Chem. 277:26310–26320. 2002.PubMed/NCBI
11	Xu XY, Yang X, Takahashi H, et al: The down-regulated SERCA3 expression is closely linked to pathogenesis, invasion, metastasis and poor prognosis of gastric carcinomas. Tumour Biol. 33:1845–1854. 2012. View Article : Google Scholar : PubMed/NCBI
12	Colorectal Cancer Facts and Figures. American Cancer Society; 2005
13	Yoshida D, Kono S, Moore MA, et al: Colorectal polypectomy and risk of colorectal cancer by subsite: the Fukuoka Colorectal Cancer study. Jpn J Clin Oncol. 37:597–602. 2007. View Article : Google Scholar : PubMed/NCBI
14	Hamilton SR and Aaltonen LA: WHO Classification of Tumors: Pathology and Genetics of Tumors of the Digestive System. IARC Press; Lyon: 2000
15	Sobin LH and Wittekind CH: TNM Classification of Malignant Tumours. 6th edition. John Wiley & Sons; Hoboken, NJ: 2002
16	Li W, Murai Y, Okada E, et al: Modified and simplified western blotting protocol: use of intermittent microwave irradiation (IMWI) and 5% skim milk to improve binding specificity. Pathol Int. 52:234–238. 2002.PubMed/NCBI
17	Kumada T, Tsuneyama K, Hatta H, Ishizawa S, et al: Improved 1-h rapid immunostaining method using intermittent microwave irradiation: practicability based on 5 years application in Toyama Medical and Pharmaceutical University Hospital. Mod Pathol. 17:1141–1149. 2004.
18	Brouland JP, Gélébart P, Kovàcs T, et al: The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis. Am J Pathol. 167:233–242. 2005. View Article : Google Scholar
19	Arbabian A, Brouland JP, Gélébart P, et al: Endoplasmic reticulum calcium pumps and cancer. Biofactors. 37:139–149. 2011. View Article : Google Scholar : PubMed/NCBI
20	Brouland JP, Valleur P and Papp B: Expression of SERCA pumps during cell differentiation and tumorigenesis: application to colonic carcinogenesis. Ann Pathol. 26:159–172. 2006. View Article : Google Scholar : PubMed/NCBI
21	Petrioli R, Licchetta A, Roviello G, et al: CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab. Cancer Invest. 3:65–71. 2012. View Article : Google Scholar
22	Lan YT, Lin JK, Lin TC, et al: Prognostic significance of perioperative change of CEA level in colorectal patients when pre-operative level is normal. Hepatogastroenterology. 59:717–720. 2012.PubMed/NCBI
23	Lin JK, Lin CC, Yang SH, et al: Early postoperative CEA level is a better prognostic indicator than is preoperative CEA level in predicting prognosis of patients with curable colorectal cancer. Int J Colorectal Dis. 26:1135–1141. 2011. View Article : Google Scholar : PubMed/NCBI
24	Yeatman TJ, Duan C, Mao W, et al: Augmentation of carcinoembryonic antigen release from intact, viable tumor cells by a factor in human serum. Ann Surg Oncol. 2:336–342. 1995. View Article : Google Scholar : PubMed/NCBI