Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma

Fang, Wei; Piao, Zhe; Buyse, Inge M.; Simón, Daniela; Sheu, Jin‐Chuan; Perucho, Manuel; Huang, Shi

doi:10.1054/bjoc.2000.1667

Cited by 29 publications

(16 citation statements)

References 24 publications

(29 reference statements)

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“…The RUNX3 gene is located on human chromosome 1p36, a region that has long been suspected to harbor one or more suppressors of various tumors [8,[12][13] . Recent studies suggested that RUNX3 has been implicated as a tumor suppressor in several tumors, including gastric cancer, colorectal cancer, hepatocellular cancer and esophageal squamous cell carcinoma among others [6,[14][15][16] .…”

Section: Discussionmentioning

confidence: 99%

Expression of RUNX3 Gene, Methylation Status and Clinicopathological Significance in Breast Cancer and Breast Cancer Cell Lines

Ying

Tong²,

Lou³

et al. 2008

Pathobiology

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Background: Runt-related transcription factor 3 (RUNX3) is a novel tumor suppressor gene that is frequently silenced by promoter hypermethylation in gastric cancer. In this study, we aimed to analyze the methylation status of the RUNX3 promoter in breast cancer and to evaluate the relationship between RUNX3 expression and breast carcinogenesis and prognosis. Methods: RT-PCR and Western blot were applied on 5 breast cancer cell lines, the human normal breast cell line Hs578Bst and 30 pairs of breast cancer and their matching normal breast tissues to detect mRNA and protein expression of the RUNX3 gene. Methylation-specific PCR was employed to detect the methylation status of the RUNX3 promoter. Immunohistochemical study was performed to analyze RUNX3 protein expression in 88 breast cancer tissues and 40 breast fibroadenomas. Results: The expression of RUNX3 mRNA and protein were negative in 3 breast cancer cell lines (T47D, MCF7 and SKBR3) as analyzed by RT-PCR and Western blotting. Hypermethylation of the RUNX3 promotor was identified in the T47D and MCF7 cell lines, but was not detected in SKBR3. Western blot analysis showed that the RUNX3 protein of 44 kDa was detected in 15 of 30 (50%) breast cancers. However, RUNX3 protein was detected in all normal breast tissues. Methylation was detected in 13 of the 15 tissues (86.67%) that did not express RUNX3 protein, but was never detected in any surrounding normal tissues. Immunohistochemistry results revealed that the positive rate of RUNX3 protein expression in breast cancer (35.23%) was much lower than that in breast fibroadenoma (85%). RUNX3 expression was correlated with tumor infiltration, clinical stage, lymph node metastasis and the expression of estrogen and progesterone receptor (p < 0.05), but was not related to age, tumor types and pathological grade (p > 0.05). The survival rate of the patients with RUNX3-positive expression was higher than that with RUNX3-negative expression (p < 0.05). Conclusions: The expression of RUNX3 gene is decreased in breast cancer. The RUNX3 gene may play an important role in the carcinogenesis of breast cancer. The mechanism of its inactivation may be hypermethylation of the promoter. With the increased progression of breast cancer, the expression of RUNX3 protein tends to decrease. The expression of RUNX3 protein has a definite value in judging prognosis in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Expression of RUNX3 Gene, Methylation Status and Clinicopathological Significance in Breast Cancer and Breast Cancer Cell Lines

Ying

Tong²,

Lou³

et al. 2008

Pathobiology

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“…Methylation Specific PCR (MSP) assay was performed according to the procedure described by Fang et al [15] . In brief, 1 μg of the genomic DNA was modified by sodium bisulfide using the CpGenome DNA Modification Kit (Intergen, Purchase, NY) in accordance with the manufacturer's instructions.…”

Section: Riz1 Promoter Methylation Specific Pcr Assaymentioning

confidence: 99%

Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration

Chen¹

2007

WJG

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AIM:To investigate the role of SMYD3 in hepatocellular carcinoma (HCC) development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS:Expression of SMYD3 in HCC cell lines and tissues were measured; silencing of SMYD3 by RNA interference (RNAi) was effectuated, hepatoma cell proliferation, migration and apoptosis were tested, with RIZ1 CpG promoter methylation, and corresponding mRNA expression were investigated. RESULTS: S M Y D 3o v e r -e x p r e s s i o n i n H C C w a s associated with RIZ1 hypermethylation and mRNA down-expression. Suppression of SMYD3 expression demethylated RIZ1 CpG promoter (P < 0.01) and increased RIZ1 mRNA expression (P < 0.01). Consequently, SMYD3 down-expression with RIZ1 de-methylation strongly inhibited hepatoma cell growth (MTT inhibitory rates: Pgenesil-1-s1 60.95% ± 7.97%, Pgenesil-1-s2 72.14%

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“…On the other hand, the RIZ2 protein is always detected or overexpressed in cancer cells. Deletions of the RIZ gene occur in breast, liver, and familial and sporadic colon cancers (Huang, 1999;Chadwick et al, 2000;Fang et al, 2001). Low or null expression of the RIZ1, but not the RIZ2, mRNA is detected in myeloid leukemia and in a large number of human cancers, including breast, liver, bone, skin melanoma, lung, colon, and neuroendocrine cancers, which suggests a selective epigenetic silencing of RIZ1 (Piao et al, 2000;Sakurada et al, 2001;Steele-Perkins et al, 2001;Poetch et al, 2002;Sasaki et al, 2002;Geli et al, 2005).…”

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confidence: 99%

Expression of RIZ1 protein (Retinoblastoma‐interacting zinc‐finger protein 1) in prostate cancer epithelial cells changes with cancer grade progression and is modulated in vitro by DHT and E2

Rossi

Staibano

Abbondanza

et al. 2009

Journal Cellular Physiology

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The nuclear protein methyl-transferase Retinoblastoma-interacting zinc-finger protein 1 (RIZ1) is considered to be a downstream effector of estrogen action in target tissues. Silencing of RIZ1 expression is common in many tumors. We analyzed RIZ1 expression in normal and malignant prostate tissue and evaluated whether estradiol (E2) or dihydrotestosterone (DHT) treatment modulated RIZ1 in cultured prostate epithelial cells (PEC). Moreover, we studied the possible involvement of RIZ1 in estrogen action on the EPN prostate cell line, constitutively expressing both estrogen receptor (ER)-alpha and beta. RIZ1 protein, found in the nucleus of normal PECs by immunohistochemistry, was progressively lost in cancer tissues as the Gleason score increased and was only detected in the cytoplasmic compartment. RIZ1 transcript levels, as assayed by semi-quantitative RT-PCR in primary PEC cultures, were significantly reduced in cancer cells (P < 0.05). In EPN DHT treatment significantly increased RIZ1 transcript and protein levels (P < 0.05); E2 induced a reduction of S phase without significant changes of RIZ1 expression. In E2-treated EPN cell extracts RIZ co-immunoprecipitated with ERbeta and ERalpha. Our data demonstrate that RIZ1 is expressed in normal PECs and down-regulated in cancer cells, with a switch of its sub-cellular localization from the nucleus to the cytoplasm upon cancer grade progression. RIZ1 expression levels in the PECs were modulated by DHT or E2 treatment in vitro. Furthermore, the E2 effects on ER-expressing prostate cells involve RIZ1, which confirms a possible role for ER-mediated pathways in a non-classic E(2)-target tissue.

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Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma

Cited by 29 publications

References 24 publications

Expression of RUNX3 Gene, Methylation Status and Clinicopathological Significance in Breast Cancer and Breast Cancer Cell Lines

Expression of RUNX3 Gene, Methylation Status and Clinicopathological Significance in Breast Cancer and Breast Cancer Cell Lines

Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration

Expression of RIZ1 protein (Retinoblastoma‐interacting zinc‐finger protein 1) in prostate cancer epithelial cells changes with cancer grade progression and is modulated in vitro by DHT and E2

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