Suppression of invasive ability of highly metastatic rat prostate cancer by introduction of human chromosome 8

Kuramochi, Hiroaki; Ichikawa, Tomohiko; Nihei, Naoki; Kawana, Youko; Suzuki, Hiroyoshi; Schalken, Jack A.; Takeichi, Masatoshi; Nagafuchi, Akira; Itô, Haruo; Shimazaki, Jun

doi:10.1002/(sici)1097-0045(19970401)31:1<14::aid-pros3>3.0.co;2-i

Cited by 14 publications

(6 citation statements)

References 24 publications

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“…In prostate cancer, loss of heterozygosity (LOH) for markers on 8p is one of the most frequent somatic mutations, occurring in >60% of these tumors (Cunningham et al 1996). Functional evidence that chromosome 8 contains tumor suppressor gene-associated activity is provided by microcell-mediated chromosome transfer studies, which demonstrate suppression by this chromosome of in vivo metastatic ability and in vitro invasiveness in the highly metastatic rat prostate cancer cell line AT6.2 (Nihei et al 1996;Kuramochi et al 1997), suppression of both tumorigenicity and in vitro invasiveness in the COKFu colon carcinoma cell line (Tanaka et al 1996), reduction of tumorigenicity in the SW620 colon carcinoma cell line, and total suppression of soft agar clonicity in the HT29 colon carcinoma cell line (Gustafson et al 1996). Together, these studies strongly suggest that 8p harbors a tumor suppressor gene involved in the genesis of epithelial malignancies.…”

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confidence: 94%

High-Resolution Physical Map and Transcript Identification of a Prostate Cancer Deletion Interval on 8p22

Arbieva¹,

Banerjee²,

Kim³

et al. 2000

Genome Res.

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A genomic interval of ∼1-1.5 Mb centered at the MSR marker on 8p22 has emerged as a possible site for a tumor suppressor gene, based on high rates of allele loss and the presence of a homozygous deletion found in metastatic prostate cancer. The objective of this study was to prepare a bacterial contig of this interval, integrate the contig with radiation hybrid (RH) databases, and use these resources to identify transcription units that might represent the candidate tumor suppressor genes. Here we present a complete bacterial contig across the interval, which was assembled using 22 published and 17 newly originated STSs. The physical map provides twofold or greater coverage over much of the interval, including 17 BACs, 15 P1s, 2 cosmids, and 1 PAC clone. The position of the selected markers across the interval in relation to the other markers on the larger chromosomal scale was confirmed by RH mapping using the Stanford G3 RH panel. Transcribed units within the deletion region were identified by exon amplification, searching of the Human Transcript Map, placement of unmapped expressed sequence tags (ESTs) from the Radiation Hybrid Database (RHdb), and from other published sources, resulting in the isolation of six unique expressed sequences. The transcript map of the deletion interval now includes two known genes (MSR and N33) and six novel ESTs.

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confidence: 94%

High-Resolution Physical Map and Transcript Identification of a Prostate Cancer Deletion Interval on 8p22

Arbieva¹,

Banerjee²,

Kim³

et al. 2000

Genome Res.

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“…Several human chromosomes, including 1,2,7,8,10,11,12,16, and 17, have been reported to contain regions of metastasis suppression activities by MMCT. Subsequently, this technique has enabled the discovery of novel genes such as KISS1, MKK4, and BRMS1 on these regions that were later proven to have clinical relevance (Ichikawa et al, 1992;Rinker-Schaeffer et al, 1994;Nihei et al, 1995Nihei et al, , 1996Nihei et al, , 1999You et al, 1995;Miele et al, 1996Miele et al, , 1997Phillips et al, 1996;Chekmareva et al, 1997;Kuramochi et al, 1997;Luu et al, 1998;Mashimo et al, 1998;Yoshida et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Identification of tumor metastasis suppressor region on the short arm of human chromosome 20

Goodarzi

Mashimo

Watabe

et al. 2001

Genes Chromosomes & Cancer

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Acquisition of metastatic ability by prostate cancer cells is the hallmark of their lethal trait and outcome. However, the genetic alterations underlying the clinical progression and pathogenesis of prostate cancer are not well understood. Several studies involving loss of heterozygosity (LOH) and comparative genomic hybridization analysis have identified distinctively altered regions on various human chromosomes, and genomic imbalance of chromosome 20 was implicated in progression and recurrence of prostate tumors. To examine the role of chromosome 20 in prostate neoplasms, we introduced this chromosome into highly metastatic rat prostate cancer cells using the microcell-mediated chromosome transfer technique. Introduction of the chromosome resulted in significant suppression of the metastatic ability of the hybrid cells, by as much as 98%, without any interference with the in vivo growth rate or tumorigenicity of primary tumor in SCID mice. Our STS-PCR analysis on 10 hybrid clones indicates that the suppressor activity of chromosome 20 is located in the p11.23-12 region. Further examination of the hybrid clones by experimental metastasis assay and histologic analysis as well as Matrigel invasion assay suggests the involvement of the suppressor region at an early stage of invasion and extravasation. We also investigated the status of the chromosome 20 suppressor region in pathology specimens from human prostate cancer patients and detected the frequent loss of this region in high-grade tumors. These results suggest the presence of a putative suppressor gene on human chromosome 20 that is functionally involved in development of prostate cancer metastases.

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“…Recent allelotyping studies have shown that allelic losses on the short arm of chromosome 8, particularly at bands [21][22], frequently are associated with various tumors, including prostate cancer (6,7), breast cancer (8), head and neck squamous cell carcinoma (9)(10)(11), urinary bladder carcinoma (12), hepatocellular carcinoma (13), and hematological malignancies (14). A recent genome-wide search for LOH in breast cancer showed that 8p is one of the most frequently altered chromosome regions (15); LOH at 8p21-22 was associated with the invasive behavior of breast cancer (16,17).…”

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confidence: 99%

“…Loss at 8p21. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] has been shown to be associated strongly with prostate cancer progression (18). These observations suggest that chromosome region 8p21-22 plays an important role in the development of various tumors, including prostate and breast cancers.…”

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confidence: 99%

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The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors

Ishii

Baffa

Numata

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

132

140

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Alterations of human chromosome 8p occur frequently in many tumors. We identified a 1.5-Mb common region of allelic loss on 8p22 by allelotype analysis. cDNA selection allowed isolation of several genes, including FEZ1. The predicted Fez1 protein contained a leucine-zipper region with similarity to the DNA-binding domain of the cAMPresponsive activating-transcription factor 5. RNA blot analysis revealed that FEZ1 gene expression was undetectable in more than 60% of epithelial tumors. Mutations were found in primary esophageal cancers and in a prostate cancer cell line. Transcript analysis from several FEZ1-expressing tumors revealed truncated mRNAs, including a frameshift. Alteration and inactivation of the FEZ1 gene may play a role in various human tumors.

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Suppression of invasive ability of highly metastatic rat prostate cancer by introduction of human chromosome 8

Cited by 14 publications

References 24 publications

High-Resolution Physical Map and Transcript Identification of a Prostate Cancer Deletion Interval on 8p22

High-Resolution Physical Map and Transcript Identification of a Prostate Cancer Deletion Interval on 8p22

Identification of tumor metastasis suppressor region on the short arm of human chromosome 20

The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors

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