Identification of a YAC from 16q24 carrying a senescence gene for breast cancer cells

De, Reddy; Cl, Keck; Popescu, N. C.; Rs, Athwal; Gp, Kaur

doi:10.1038/sj.onc.1203264

Cited by 12 publications

(17 citation statements)

References 35 publications

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“…Even tumors that have arisen through multiple genetic alterations on di erent chromosomes have been reverted to a less tumorigenic phenotype, indicating that introduction of a single TSG may be su cient to suppress tumor growth. More recently, functional complementation using YAC clones has been used successfully to further localize putative TSGs to individual YACs, which are more amenable to positional cloning approaches (Koreth et al, 1999;Murakami et al, 1998;Reddy et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22

et al. 2001

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Deletions in the 8p21-22 region of the human genome are among the most common genetic alterations in prostate carcinomas. Several studies in di erent tumor tissues, including prostate, indicate that there are probably multiple tumor suppressor genes (TSGs) present in this region. To identify candidate TSGs on 8p22 a YAC contig spanning this region was assembled and YAC clones retro®tted with a selectable marker (neo) were transferred into rat prostate AT6.2 cells. Two overlapping YAC clones showed greatly reduced colonyforming e ciency, indicating they may carry a TSG. Two BAC clones encompassing the overlapping region also appeared to exert suppressive e ects on the growth of AT6.2 cells. Database searches for genes mapped to the critical region identi®ed a gene known as FEZ1 (LZTS1) as a potential candidate suppressor gene. Subsequent experiments showed that over-expression of LZTS1 cDNA inhibited stable colony-forming e ciencies of AT6.2, HEK-293 and LNCaP cells. In contrast, LZTS1-transfected Rat-1 and RM1 cells were growthstimulated. Database searches also identi®ed additional isoforms of the LZTS1 mRNA, as well as LZTS1 protein domains reminiscent of those found in transcription factors. Together these data suggest that the LZTS1 gene is involved in the regulation of cell growth and its loss of function may contribute to the development of prostatic carcinomas, as well as other cancers. Oncogene (2001) 20, 4169 ± 4179.

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Section: Introductionmentioning

confidence: 99%

Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22

et al. 2001

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“…The precise positional information allowed us to identify candidate Yeast Artificial Chromosome (YAC) clones, which may carry the SEN16 locus. The functional testing of individual YAC clones, located at 16q24.3, led to the identification of a single 360 kb YAC that carries the SEN16 gene (Reddy et al, 2000). This paper reports the identification of an 85 kb BAC clone that carries the SEN16 gene, by functional complementation of immortal breast tumor cells.…”

Section: Introductionmentioning

confidence: 99%

“…Four of the BAC clones in Figure 1 overlay YAC792E1, which was previously shown to induce senescence in immortal breast tumor cell lines (Reddy et al, 2000). The 150 kb insert of 344A17 and the slightly larger insert of 178L8 both carry all seven STS markers mapped to the 360 kb insert of YAC792E1.…”

Section: Construction Of a Bac Contig At The Sen16 Locusmentioning

confidence: 99%

“…The 150 kb insert of 344A17 and the slightly larger insert of 178L8 both carry all seven STS markers mapped to the 360 kb insert of YAC792E1. The 85 kb insert of 346J21 carries four markers from the left side of YAC792E1, which are associated with senescence activity (Reddy et al, 2000).…”

Section: Construction Of a Bac Contig At The Sen16 Locusmentioning

confidence: 99%

“…Applying this approach, we have previously identified cell senescence loci on human chromosomes 6 and 16 (Sandhu et al, 1994(Sandhu et al, , 1996Reddy et al, 1999Reddy et al, , 2000. Chromosome 16 is of particular interest because an abundance of evidence points to the presence of multiple tumor suppressor genes on the long arm of 16.…”

Section: Introductionmentioning

confidence: 99%

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Functional identification of a BAC clone from 16q24 carrying a senescence gene SEN16 for breast cancer cells

et al. 2004

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We have identified an 85 kb BAC clone, 346J21, that carries a cell senescence gene (SEN16), previously mapped to 16q24.3. Transfer and retention of 346J21 in breast cancer cell lines leads to growth arrest after 8-10 cell doublings, accompanied by the appearance of characteristic senescent cell morphology and senescence-associated acid b-galactosidase activity. Loss of transferred BAC results in reversion to the immortal growth phenotype of the parental cancer cell lines. BAC 346J21 restores senescence in the human breast cancer cell lines, MCF.7 and MDA-MB468, and the rat mammary tumor cell line LA7, but not in the human glioblastoma cell line T98G. We postulate that inactivation of both copies of SEN16 is required for the immortalization of breast epithelial cells at an early stage of tumorigenesis. Positional mapping of 346J21 shows that SEN16 is distinct from other candidate tumor suppressor genes reported at 16q24.

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Chromosome and gene alterations in breast cancer as markers for diagnosis and prognosis as well as pathogenetic targets for therapy

Popescu

Zimonjic

2002

Am. J. Med. Genet.

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Chromosomal abnormalities have been implicated in cancer development since the turn of the last century. Only during the past two decades, with advances in cytogenetics and molecular biology, has the genetic basis of neoplasia been firmly established, however, with chromosomal alterations being recognized as critical in the pathogenesis of human cancer. Recurrent chromosomal alterations provide cytological and molecular markers for the diagnosis and prognosis of disease. They also facilitate the identification of genes that are important in carcinogenesis and, ultimately, may lead to the development of targeted therapy. In breast cancer, the most prevalent malignancy among females, substantial progress has been achieved in identifying genes located at sites of recurrent chromosomal alterations and in profiling gene expression through the application of powerful cytogenetic and functional genomic techniques. Characterization of the molecular pathologic characteristics and gene-expression profiles of breast cancer should provide new clinical tools for the accurate diagnosis and prediction of prognosis as well as new targets for the development of therapeutic agents.

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Identification of a YAC from 16q24 carrying a senescence gene for breast cancer cells

Cited by 12 publications

References 35 publications

Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22

Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22

Functional identification of a BAC clone from 16q24 carrying a senescence gene SEN16 for breast cancer cells

Chromosome and gene alterations in breast cancer as markers for diagnosis and prognosis as well as pathogenetic targets for therapy

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