Identification and Characterization of Tropomyosin 3 Associated with Granulin-epithelin Precursor in Human Hepatocellular Carcinoma

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jul 14

PMID 22792281

Citations 21

Authors

Ching Yan Lam

Chi Wai Yip

Terence C W Poon

Christine K C Cheng

Eddy W Y Ng

Nicholas C L Wong

Phyllis F Y Cheung

Paul B S Lai

Irene O L Ng

Sheung Tat Fan

Siu Tim Cheung

Affiliations

Soon will be listed here.

Abstract

Background And Aim: Granulin-epithelin precursor (GEP) has previously been reported to control cancer growth, invasion, chemo-resistance, and served as novel therapeutic target for cancer treatment. However, the nature and characteristics of GEP interacting partner remain unclear. The present study aims to identify and characterize the novel predominant interacting partner of GEP using co-immunoprecipitation and mass spectrometry.

Methods And Results: Specific anti-GEP monoclonal antibody was used to capture GEP and its interacting partner from the protein extract of the liver cancer cells Hep3B. The precipitated proteins were analyzed by SDS-PAGE, followed by mass spectrometry and the protein identity was demonstrated to be tropomyosin 3 (TPM3). The interaction has been validated in additional cell models using anti-TPM3 antibody and immunoblot to confirm GEP as the interacting partner. GEP and TPM3 expressions were then examined by real-time quantitative RT-PCR in clinical samples, and their transcript levels were significantly correlated. Elevated TPM3 levels were observed in liver cancer compared with the adjacent non-tumorous liver, and patients with elevated TPM3 levels were shown to have poor recurrence-free survival. Protein expression of GEP and TPM3 was observed only in the cytoplasm of liver cancer cells by immunohistochemical staining.

Conclusions: TPM3 is an interacting partner of GEP and may play an important role in hepatocarcinogenesis.

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