Skip to main content
Top
Published in: Medical Oncology 2/2012

01-06-2012 | Original Paper

Phospholipase C epsilon plays a suppressive role in incidence of colorectal cancer

Authors: Xiaoliang Wang, Chongzhi Zhou, Guoqiang Qiu, Yinxue Yang, Dongwang Yan, Tonghai Xing, Junwei Fan, Huamei Tang, Zhihai Peng

Published in: Medical Oncology | Issue 2/2012

Login to get access

Abstract

In our previous study, we have found that PLCE1 was down-regulated in sporadic colorectal cancer. But the role of PLCE1 in the incidence of colorectal cancer is still not definite. Therefore, in order to validate whether PLCE1 displays a suppressive role, in this study, we examined the expression of PLCE1 in sporadic colorectal cancer with a larger sample size and the effect of PLCE1 overexpression on cancer cell malignant degree. The expression level of PLCE1 in 50 colorectal cancers with their pair-matched normal tissues was measured by RT-PCR, Western blot, and immunohistochemistry. The effect of PLCE1 overexpression on cancer cell malignant degree was measured by MTT assay, plate colony formation assay, soft agar colony formation assay, cell cycle and apoptosis analysis, and xenograft assay. We found that PLCE1 was down-regulated in 42% (21/50) of colorectal cancer tissues compared with pair-matched normal tissues, more frequent in the poor differentiation tumor in patients under 60. Overexpression of PLCE1 significantly inhibited the proliferation of colon cancer cells and degraded its malignant degree. These results suggest that PLCE1 may be involved in the development of sporadic colorectal cancer through its inhibitory effect on cell proliferation. PLCE1 exhibits a suppressive role in incidence of colorectal cancer.
Literature
1.
go back to reference Goel A, Boland CR. Recent insights into the pathogenesis of colorectal cancer. Curr Opin Gastroentero. 2010;26:47–52.CrossRef Goel A, Boland CR. Recent insights into the pathogenesis of colorectal cancer. Curr Opin Gastroentero. 2010;26:47–52.CrossRef
2.
go back to reference Wang X, Zhou C, Qiu G, Fan J, Tang H, et al. Screening of new tumor suppressor genes in sporadic colorectal cancer patients. Hepato-Gastroenterol. 2008;55:2039–44. Wang X, Zhou C, Qiu G, Fan J, Tang H, et al. Screening of new tumor suppressor genes in sporadic colorectal cancer patients. Hepato-Gastroenterol. 2008;55:2039–44.
3.
go back to reference Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW. A novel bifunctional phospholipase C that is regulated by Galpha(12) and stimulates the Ras/mitogen-activated protein kinase pathway. J Biol Chem. 2001;276:2758–65.PubMedCrossRef Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW. A novel bifunctional phospholipase C that is regulated by Galpha(12) and stimulates the Ras/mitogen-activated protein kinase pathway. J Biol Chem. 2001;276:2758–65.PubMedCrossRef
4.
go back to reference Citro S, Malik S, Oestreich EA, Radeff-Huang J, Kelley GG, et al. Phospholipase C epsilon is a nexus for Rho and Rap-mediated G protein-coupled receptor-induced astrocyte proliferation. Proc Natl Acad Sci USA. 2007;104:15543–8.PubMedCrossRef Citro S, Malik S, Oestreich EA, Radeff-Huang J, Kelley GG, et al. Phospholipase C epsilon is a nexus for Rho and Rap-mediated G protein-coupled receptor-induced astrocyte proliferation. Proc Natl Acad Sci USA. 2007;104:15543–8.PubMedCrossRef
5.
go back to reference Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116:1453–6.PubMedCrossRef Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116:1453–6.PubMedCrossRef
6.
go back to reference Shibatohge M, Kariya K, Liao Y, Hu CD, Watari Y, et al. Identification of PLC210, a caenorhabditis elegans phospholipase C, as a putative effector of Ras. J Biol Chem. 1998;273:6218–22.PubMedCrossRef Shibatohge M, Kariya K, Liao Y, Hu CD, Watari Y, et al. Identification of PLC210, a caenorhabditis elegans phospholipase C, as a putative effector of Ras. J Biol Chem. 1998;273:6218–22.PubMedCrossRef
7.
go back to reference Harden TK, Sondek J. Regulation of phospholipase C isozymes by ras superfamily GTPases. Annu Rev Pharmacol Toxicol. 2006;46:355–79.PubMedCrossRef Harden TK, Sondek J. Regulation of phospholipase C isozymes by ras superfamily GTPases. Annu Rev Pharmacol Toxicol. 2006;46:355–79.PubMedCrossRef
8.
go back to reference Ada-Nguema AS, Xenias H, Hofman JM, Wiggins CH, Sheetz MP, et al. The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLC epsilon. J Cell Sci. 2006;119:1307–19.PubMedCrossRef Ada-Nguema AS, Xenias H, Hofman JM, Wiggins CH, Sheetz MP, et al. The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLC epsilon. J Cell Sci. 2006;119:1307–19.PubMedCrossRef
9.
go back to reference Jin TG, Satoh T, Liao Y, Song C, Gao X, et al. Role of the CDC25 homology domain of phospholipase C epsilon in amplification of Rapl-dependent signaling. J Biol Chem. 2001;276:30301–7.PubMedCrossRef Jin TG, Satoh T, Liao Y, Song C, Gao X, et al. Role of the CDC25 homology domain of phospholipase C epsilon in amplification of Rapl-dependent signaling. J Biol Chem. 2001;276:30301–7.PubMedCrossRef
10.
go back to reference Kelley GG, Reks SE, Ondrako JM, Smrcka AV. Phospholipase C(epsilon): a novel Ras effector. EMBO J. 2001;20:743–54.PubMedCrossRef Kelley GG, Reks SE, Ondrako JM, Smrcka AV. Phospholipase C(epsilon): a novel Ras effector. EMBO J. 2001;20:743–54.PubMedCrossRef
11.
go back to reference Somg C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, et al. Regulation of a novel human phospholipase C, PLC epsilon, through membrane targeting by Ras. J Biol Chem. 2001;276:2752–7.CrossRef Somg C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, et al. Regulation of a novel human phospholipase C, PLC epsilon, through membrane targeting by Ras. J Biol Chem. 2001;276:2752–7.CrossRef
12.
13.
go back to reference Hesson L, Dallol A, Minna JD, Maher ER, Latif F, et al. A homologue of RASSF1A tumour suppressor gene is inactivated in human cancers. Oncogene. 2003;22:947–54.PubMedCrossRef Hesson L, Dallol A, Minna JD, Maher ER, Latif F, et al. A homologue of RASSF1A tumour suppressor gene is inactivated in human cancers. Oncogene. 2003;22:947–54.PubMedCrossRef
14.
go back to reference Allen NP, Donninger H, Vos MD, Eckfeld K, Hesson L, et al. RASSF6 is a novel member of the RASSF family of tumor suppressors. Oncogene. 2007;26:6203–11.PubMedCrossRef Allen NP, Donninger H, Vos MD, Eckfeld K, Hesson L, et al. RASSF6 is a novel member of the RASSF family of tumor suppressors. Oncogene. 2007;26:6203–11.PubMedCrossRef
15.
go back to reference Maruyama R, Akino K, Toyota M, Suzuki H, Imai T, et al. Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer. Carcinogenesis. 2008;29:1312–8.PubMedCrossRef Maruyama R, Akino K, Toyota M, Suzuki H, Imai T, et al. Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer. Carcinogenesis. 2008;29:1312–8.PubMedCrossRef
16.
go back to reference Imai T, Toyota M, Suzuki H, Akino K, Ogi K, et al. Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma. Cancer Sci. 2008;99:958–66.PubMedCrossRef Imai T, Toyota M, Suzuki H, Akino K, Ogi K, et al. Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma. Cancer Sci. 2008;99:958–66.PubMedCrossRef
17.
go back to reference Avruch J, Xavier R, Bardeesy N, Zhang XF, Praskova M, et al. Rassf family of tumor suppressor polypeptides. J Biol Chem. 2009;284:11001–5.PubMedCrossRef Avruch J, Xavier R, Bardeesy N, Zhang XF, Praskova M, et al. Rassf family of tumor suppressor polypeptides. J Biol Chem. 2009;284:11001–5.PubMedCrossRef
18.
go back to reference Stieglitz B, Bee C, Schwarz D, Yildiz O, Moshnikova A, et al. Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II. EMBO J. 2008;27:1995–2005.PubMedCrossRef Stieglitz B, Bee C, Schwarz D, Yildiz O, Moshnikova A, et al. Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II. EMBO J. 2008;27:1995–2005.PubMedCrossRef
19.
go back to reference Ikeda M, Hirabayashi S, Fujiwara N, Mori H, Kawata A, et al. Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways. Exp Cell Res. 2007;313:1484–95.PubMedCrossRef Ikeda M, Hirabayashi S, Fujiwara N, Mori H, Kawata A, et al. Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways. Exp Cell Res. 2007;313:1484–95.PubMedCrossRef
Metadata
Title
Phospholipase C epsilon plays a suppressive role in incidence of colorectal cancer
Authors
Xiaoliang Wang
Chongzhi Zhou
Guoqiang Qiu
Yinxue Yang
Dongwang Yan
Tonghai Xing
Junwei Fan
Huamei Tang
Zhihai Peng
Publication date
01-06-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9981-1

Other articles of this Issue 2/2012

Medical Oncology 2/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.