RESEARCH PAPER
DLC3 expression in hepatocellular carcinoma
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Department of Pathology, Medical University of Warsaw, Warsaw, Poland
Corresponding author
Ewa Wolinska
Department of Pathology, Medical University, Warsaw, Zwirki i Wigury 61, 02–091 Warsaw, Poland
J Pre Clin Clin Res. 2015;9(2):105-108
KEYWORDS
ABSTRACT
Introduction and objective:
Deleted in Liver Cancer (DLC) proteins belong to the family of RhoGAPs and thus are believed to operate as negative regulators of the Rho family of small GTPases. Rho proteins are considered to be significant links between numerous cellular pathways. So far, DLC1 – the first identified member from Deleted in Liver Cancer family – has been established as a tumour suppressor in hepatocellular carcinoma. As shown by many studies, DLC1 expression is reduced by gene loss or epigenetic silencing in this type of cancer. The expression and function of its close family relative DLC3 is less known. The presented study determined the expression and cellular localization of DLC3 protein in hepatocellular carcinoma tissue.
Material and Methods:
The protein level in two types of hepatocellular carcinoma: typical and fibrolamellar, were assessed by the immunohistochemical approach.
Results:
DLC3 immunoreactivity was found to be present in the cytoplasm of normal hepatocytes. In hepatocellular carcinoma sections, DLC3 was detected primarily in the cytoplasm of cancer cells, although in a small percentage of cancer cells cell nuclei were also positively stained. Morphometric analysis followed by statistical evaluation showed that the DLC3 immunoreactivity in the tumour sections was comparable to the one observed in non-cancerous liver specimens.
Conclusions:
The results obtained indicate that DLC3 protein, contrary to DLC1, is commonly expressed in hepatocellular carcinoma. It appears that members of the DLC family, although structurally highly related, may function differently during HCC development.
REFERENCES (14)
1.
Heasman SJ, Ridley AJ. Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol. 2008; 9: 690–701.
2.
Ellenbroek SI, Collard JG. Rho GTPases: functions and association with cancer. Clin Exp Metastasis. 2007; 24: 657–672.
3.
Zimonjic DB, Popescu NC. Role of DLC1 tumour suppressor gene and MYC oncogene in pathogenesis of human hepatocellular carcinoma: potential prospects for combined targeted therapeutics (review). Int J Oncol. 2012; 41: 393–406.
4.
Durkin ME, Ullmannova V, Guan M, Popescu NC. Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumour cell growth. Oncogene 2007; 26: 4580–4589.
5.
Kawai K, Kiyota M, Seike J, Deki Y, Yagisawa H. START-GAP3/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology. Biochem Biophys Res Commun. 2007; 364: 783–789.
6.
Leonardi GC, Candido S, Cervello M, Nicolosi D, Raiti F, Travali S, et al. The tumour microenvironment in hepatocellular carcinoma (review). Int J Oncol. 2012; 40: 1733–1747.
7.
Sanyal AJ, Yoon SK, Lencioni R. The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist 2010; 15 Suppl 4: 14–22.
8.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359: 378–390.
9.
Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008; 48 Suppl 1: S20–37.
10.
Kakar S, Burgart LJ, Batts KP, Garcia J, Jain D, Ferrell LD. Clinicopathologic features and survival in fibrolamellar carcinoma: comparison with conventional hepatocellular carcinoma with and without cirrhosis. Mod Pathol. 2005; 18: 1417–1423.
11.
Chan LK, Ko FC, Sze KM, Ng IO, Yam JW. Nuclear-targeted deleted in liver cancer 1 (DLC1) is less efficient in exerting its tumour suppressive activity both in vitro and in vivo. PLoS One 2011; 6: e25547.
12.
Dubash AD, Guilluy C, Srougi MC, Boulter E, Burridge K, Garcia-Mata R. The small GTPase RhoA localizes to the nucleus and is activated by Net1 and DNA damage signals. PLoS One 2011; 6: e17380.
13.
Hervy M, Hoffman L, Beckerle MC. From the membrane to the nucleus and back again: bifunctional focal adhesion proteins. Curr Opin Cell Biol. 2006; 18: 524–532.
14.
Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, et al. The consensus coding sequences of human breast and colorectal cancers. Science 2006; 314: 268–274.