Chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma when high and low metastatic models are compared

Qin, Lun–Xiu; Tang, Zhao–You; Ye, S. L.; Liu, Y. K.; C., Z.; Zhou, Xiaoyan; Wu, Zhiyuan; Sun, Feiyu; Tian, Jianqiu; Guan, Xin‐Yuan; Pack, Svetlana D.; Zhuang, Zhengping

doi:10.1007/s004320100236

Cited by 37 publications

(34 citation statements)

References 22 publications

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“…In our recent studies, we found that chromosome 8p deletion might contribute to HCC metastasis (Qin et al, 1999). This result was further confirmed by comparisons in nude mice models of HCC with different metastatic potentials (Qin et al, 2001). In addition, a more accurate location was identified on 8p23.3 and 8p11.2 (Zhang et al, 2003).…”

Section: Introductionsupporting

confidence: 54%

“…These specific genomic aberrations could be used for mapping tumor suppressor genes (Thiagalin- In our previous studies, we found that HCC acquired a deletion on chromosome 8p during progression to the metastatic stage and chromosome 8p deletion might contribute to HCC metastasis (Qin et al, 1999). This result was confirmed in a study of the metastatic model of HCC and its cell line (Qin et al, 2001). Using genomewide microsatellite analysis, this deletion on chromosome 8p was further proved to be related to the progression and metastasis of HCC, and 8p23.3 and 8p11.2 were two likely regions harboring metastasisrelated genes (Zhang et al, 2003).…”

Section: Discussionmentioning

confidence: 60%

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HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma

Wang

et al. 2005

Oncogene

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Our previous studies suggested that chromosome 8p deletion is associated with metastasis of hepatocellular carcinoma (HCC), in which some novel metastasis suppressor genes might be harbored. The present study aimed to identify the metastatic suppressor gene(s). A cDNA chip was constructed with the expressed sequence tags (ESTs) from chromosome 8p and used to compare the difference of expression profiling between the MHCC97-H and MHCC97-L cell lines with different metastatic potentials and similar genetic backgrounds. In all, 10 ESTs were significantly downregulated in MHCC97-H cell line with higher metastatic potential. One full-length gene, HTPAP (phosphatidic acid phosphatase type 2 domain containing 1B), was identified at chromosome 8p12. Sequencing and bioinformatic analyses revealed that HTPAP has 826 bp and encodes a putative protein of 175 amino acids with a transmembrane segment at the NH2 terminus, two protein kinase C phosphorylation site and one tyrosine kinase phosphorylation site. Its expression level in metastatic tumor tissues was much lower than that of primary HCC tissues. Both in vitro and in vivo assays suggested that HTPAP could suppress the invasion and metastasis of HCC. These suggested that HTPAP is a novel metastatic suppressor gene for HCC. The mechanism of the effect of HTPAP on HCC metastasis is not clear yet and deserves further investigation.

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Section: Introductionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 60%

HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma

Wang

et al. 2005

Oncogene

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“…Loss of chromosome 8p has also been associated with metastasis in various models of HCC with a high or low metastatic potential (Qin et al, 1999;Qin et al, 2001). Although the Focus and 7703K HCC cell lines used in the present study grow rapidly in culture, they are not derived from metastases (He et al, 1984).…”

Section: Discussionmentioning

confidence: 85%

Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells

2003

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The gene deleted in liver cancer-1 (DLC-1) is located on human chromosome 8p21-22, a region thought to harbor tumor suppressor genes on the basis of its frequent deletion or loss of heterozygosity in a variety of human cancers, including hepatocellular carcinoma (HCC). Deletion or altered expression of DLC-1 is common in HCC. In the current study, the subcellular localization of Dlc-1 protein was determined by immunostaining with antibody to DLC-1 and the possible tumor growth suppressor activity of DLC-1 was investigated by examining the effects of of DLC-1 cDNA transfection in two human HCC cell lines lacking expression of the endogenous gene. The results show that Dlc-1protein is localized in the cell cytoplasm, and the restoration of DLC-1 expression in HCC cells resulted in caspase-3-mediated apoptosis, inhibition of cell growth and invasiveness in vitro as well as in reduction of the ability of the cells to form tumors in athymic nude mice. These observations thus support the notion that Dlc-1 protein is involved in hepatocarcinogenesis and has oncosuppressive activity in HCC.

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“…Similarly, LOH at 8p21-22 in HCC, breast, and prostate carcinomas was associated with an invasive tumor phenotype and metastasis (Yaremko et al, 1998;Jenkins et al, 1998;Qin et al, 2001). Interestingly, two isogenic breast cancer cell lines with diametrically opposite metastatic capabilities were derived from MDA-MB-435 cells.…”

Section: Discussionmentioning

confidence: 99%

DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity

et al. 2003

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The human DLC-1 (deleted in liver cancer 1) gene was cloned from a primary human hepatocellular carcinoma (HCC) and mapped to the chromosome 8p21-22 region frequently deleted in common human cancers and suspected to harbor tumor suppressor genes. DLC-1 was found to be deleted or downregulated in a significant number of HCCs. We expanded our investigations to other cancers with recurrent deletions of 8p22, and in this study examined alterations of DLC-1 in primary human breast tumors, human breast, colon, and prostate tumor cell lines. Genomic deletion of DLC-1 was observed in 40% of primary breast tumors, whereas reduced or undetectable levels of DLC-1 mRNA were seen in 70% of breast, 70% of colon, and 50% of prostate tumor cell lines To see whether DLC-1 expression affects cell growth and tumorigenicity, two breast carcinoma cell lines lacking the expression of endogenous gene were transfected with the DLC-1 cDNA. In both cell lines, DLC-1 transfection caused significant growth inhibition and reduction of colony formation. Furthermore, introduction of the DLC-1 cDNA abolished the in vivo tumorigenicity in nude mice, suggesting that the DLC-1 gene plays a role in breast cancer by acting as a bona fide tumor suppressor gene.

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Chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma when high and low metastatic models are compared

Cited by 37 publications

References 22 publications

HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma

HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma

Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells

DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity

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