EBAG9/RCAS1 expression in hepatocellular carcinoma: Correlation with tumor dedifferentiation and proliferation

Aoki, Teruaki; Inoue, Satoshi; Imamura, Hiroshi; Fukushima, Junichi; Urano, Tomohiko; Hasegawa, Kanae; Makuuchi, Masatoshi

doi:10.1016/s0168-8278(03)80308-2

Cited by 15 publications

(30 citation statements)

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“…RCAS1 localization patterns were significantly correlated with primary tumor size, stage grouping and malignancy. Differences in RCAS1 localization patterns have been observed in human breast cancer, hepatocellular carcinoma and gastric cancer [2,16,26]. Similar findings have also been reported for some cancer-associated antigens, including carcinoembrionic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) [8,11].…”

Section: Discussionsupporting

confidence: 74%

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Expression of a Tumor-Associated Antigen, RCAS1, in Canine Mammary Tumors

et al. 2004

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ABSTRACT. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), one of novel cancer cell-surface antigens, is strongly expressed in invasive cancers. RCAS1 inhibits the in vitro growth of lymphocytes such as T cells and natural killer (NK) cells, and induces apoptotic cell death. We investigated the expression of RCAS1 in canine mammary tumor cell lines and tumor cells by immunohistochemistry, and also in situ deoxyribonucleic acid (DNA) fragmentation in tumor-infiltrating lymphocytes (TILs) by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. All canine mammary tumor cell lines expressed RCAS1 at both the messenger ribonucleic acid (mRNA) and protein level. Immunohistochemically, RCAS1 was negative in 100% of normal mammary glands, but was expressed in 100% of malignant tumors examined. In most malignant mammary tumors, RCAS1 was localized in the cytoplasm with no polarity of expression. In benign mammary tumors, it was detected on the luminal surface of the tumor cell. RCAS1 expression or localization was significantly correlated with malignancy. In situ DNA fragmentation of CD3-positive TILs was observed in RCAS1-expressing tumors. RCAS1-expressing tumors, indicating a possible induction of apoptotic cell death in TILs through RCAS1 expression. These observations suggest that RCAS1 probably plays an important role in tumor progression and escape from immune surveillance in canine mammary tumors. KEY WORDS: canine mammary tumor, DNA fragmentation, immunohistochemistry, receptor-binding cancer antigen expressed on SiSo cells (RCAS1), tumor infiltrating lymphocyte (TILs).

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Section: Discussionsupporting

confidence: 74%

“…RCAS1 has also been detected in nongynecological cancers such as human breast carcinomas [26,32,36], esophageal squamous cell carcinomas [19], gastric adenocarcinomas [6,16], hepatocellular carcinomas [2,21], lung cancers [13,14,22], and pancreatic adenocarcinomas [1,19]. Expression of RCAS1 is associated with a poor prognosis in these cancer patients.…”

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confidence: 99%

Expression of a Tumor-Associated Antigen, RCAS1, in Canine Mammary Tumors

et al. 2004

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“…The protein expression of EBAG9 is estrogen inducible, as it has been shown in ovariectomized mice treated with 17h-estradiol administration (2). The physiologic function of EBAG9 has not been well defined, yet the molecule may be implicated in cancer pathophysiology, with several lines of evidence of the protein expression in malignancies, including breast (3), ovarian (4), prostate (5), and hepatocellular carcinomas (6). In prostate cancer (5), EBAG9 expression significantly correlated with advanced pathologic stages and high Gleason score (P = 0.0305 and P < 0.0001, respectively), suggesting the abundance of EBAG9 may relate to the progression of malignant tumors.…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor–Binding Fragment–Associated Antigen 9 Is a Tumor-Promoting and Prognostic Factor for Renal Cell Carcinoma

Ogushi¹,

Takahashi²,

Takeuchi³

et al. 2005

Cancer Research

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The estrogen receptor-binding fragment-associated antigen 9 (EBAG9) has been identified as a primary estrogenresponsive gene in human breast cancer MCF7 cells. A high expression of EBAG9 has been observed in invasive breast cancer and advanced prostate cancer, suggesting a tumorpromoting role of the protein in malignancies. Here we show that intratumoral (i.t.) administration of small interfering RNA against EBAG9 exerted overt regression of tumors following s.c. implantation of murine renal cell carcinoma (RCC) Renca cells. Overexpression of EBAG9 did not promote the proliferation of culture Renca cells; however, the inoculated Renca cells harboring EBAG9 (Renca-EBAG9) in BALB/c mice grew faster and developed larger tumors compared with Renca cells expressing vector alone (Rencavector). After renal subcapsular implantation, Renca-EBAG9 tumors significantly enlarged compared with Renca-vector tumors in BALB/c mice, whereas both Renca-EBAG9 and Renca-vector tumors were developed with similar volumes in BALB/c nude mice. No apparent difference was observed in specific cytotoxic T-cell responses against Renca-EBAG9 and Renca-vector cells; nonetheless, the number of infiltrating CD8 + T lymphocytes was decreased in Renca-EBAG9 subcapsular tumors. Furthermore, immunohistochemical study of EBAG9 in 78 human RCC specimens showed that intense and diffuse cytoplasmic immunostaining was observed in 87% of the cases and positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients. Multivariate analysis revealed that high EBAG9 expression was an independent prognostic predictor for disease-specific survival (P = 0.0485). Our results suggest that EBAG9 is a crucial regulator of tumor progression and a potential prognostic marker for RCC. (Cancer Res 2005; 65(9): 3700-6)

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“…Enhanced ·-taxilin expression in HCCs was also significantly correlated with less-differentiated histological grade, and more invasive characteristics indicated by positivity for vascular invasion and/or intrahepatic metastasis (21,22). Dedifferentiation of HCCs is usually considered to be associated with higher proliferative activity of the tumor and higher risk of vascular invasion and metastases (2).…”

Section: Discussionmentioning

confidence: 99%

Expression of α-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor

Tomiya¹

2010

Int J Oncol

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Abstract. The membrane traffic system has been recognized to be involved in carcinogenesis and tumor progression in several types of tumors. ·-taxilin is a newly identified membrane traffic-related molecule, and its up-regulation has been reported in embryonic and malignant tissues of neural origin. In the present study, we analyzed the expression of ·-taxilin in relation to clinicopathological features of hepatocellular carcinomas (HCC) and proliferative activity of the tumor determined by proliferating cell nuclear antigen labeling index (PCNA-LI). Twenty-nine surgically resected nodules of HCC (8 well-, 11 moderately-, and 10 poorlydifferentiated) were studied. Fifteen cases showed 'strong staining', while 14 cases showed 'weak staining' for ·-taxilin. A significantly higher expression of ·-taxilin was observed in less-differentiated (p=0.005), and more invasive (p=0.016) HCCs. The 'strong staining' group showed significantly higher PCNA-LI than the 'weak staining' group (the medians of PCNA-LI were 59.4% vs. 14.4%, p<0.0001). We also evaluated the expression of ·-taxilin in hepatoma cell lines (PLC/PRF/5, Hep G2 and HuH-6) in association with cell proliferation. The expression levels of ·-taxilin protein were correlated with their growth rates. In conclusion, the expression of the ·-taxilin protein was related with an increased proliferative activity and a less-differentiated histological grade of HCC. ·-taxilin may be involved in cell proliferation of HCC, and its expression can be a marker of malignant potential of HCC.

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EBAG9/RCAS1 expression in hepatocellular carcinoma: Correlation with tumor dedifferentiation and proliferation

Cited by 15 publications

References 0 publications

Expression of a Tumor-Associated Antigen, RCAS1, in Canine Mammary Tumors

Expression of a Tumor-Associated Antigen, RCAS1, in Canine Mammary Tumors

Estrogen Receptor–Binding Fragment–Associated Antigen 9 Is a Tumor-Promoting and Prognostic Factor for Renal Cell Carcinoma

Expression of α-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor

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