Direct correlation between FRA3B expression and cigarette smoking

Stein, Constance K.; Glover, Thomas W.; Palmer, J. Lynn; Glisson, Bonnie S.

doi:10.1002/gcc.10061

Cited by 62 publications

(53 citation statements)

References 40 publications

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“…21 It has also been shown that exposure to environmental carcinogens such as smoking and alcohol consumption increases the potential for chromosome breakage at fragile sites FRA3B and FRA16D in esophageal, non-small-cell lung and cutaneous squamous cancer. [21][22][23][24][25] Furthermore, we have recently described alterations on WWOX gene in 50% of oral squamous cell carcinomas. 26 Therefore, given that OLs have been associated with squamous carcinomas, we investigated whether molecular changes of the WWOX gene were present in these potentially malignant disorders.…”

Section: Introductionmentioning

confidence: 99%

Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias

et al. 2008

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SummaryOral leukoplakia is the most prevalent and potentially malignant disorder of the oral mucosa. Previous studies have demonstrated that molecular changes of the WWOX gene (WW-domain containing oxidoreductase), a candidate tumor suppressor gene located at 16q23.3-24.1 that spans FRA16D, the second most common fragile site, are present in several malignant neoplasias, including oral squamous cell carcinoma. In this report, the role of the WWOX gene was investigated in 23 cases of oral leukoplakias. Using nested RT-PCR and immunohistochemistry, altered mRNA transcription and/or reduced Wwox protein expression was observed in 35% of the lesions when compared with normal mucosa. The majority of lesions (4/6) with altered transcripts had a reduction in the expression of Wwox protein. Although normal WWOX expression was found in some lesions with dysplasia, all lesions with WWOX mRNA and/or protein expression showed histological evidence of dysplasia and none of the cases without dysplasia presented this alteration. These results show that the WWOX gene alteration is an early genetic alteration and may contribute to oral carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias

et al. 2008

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“…Re-expression of Fhit in Fhit-negative cancerderived cell lines increases sensitivity to mitomycin C (MMC), camptothecin (CPT), and cisplatin. 13,15,70,71 While the canonical role of each drug involves modulation of DNA topography to induce DNA damage, 16,17,[72][73][74] each agent also effects ROS production, and the production of ROS has been demonstrated to underlie the toxic effect of each compound.…”

Section: Discussionmentioning

confidence: 99%

“…HBEC3-TK is an immortalized bronchial epithelial cell line that has been used to study the consequences of gene inactivation in lung cancer. 13,35 These cells display normal epithelial morphology, are not transformed, have an intact p53 pathway, and have been used by others to study the pathogenesis of lung cancer. 35,36,39 We first determined that treatment of HBEC3-TK cells with 2 unique siRNAs robustly silences FHIT expression at both the mRNA and protein level ( Fig.…”

Section: Gene Expression Changes In Response To Fhit Knockdownmentioning

confidence: 99%

“…Furthermore, peripheral blood samples show that active smokers express fragility at the FHIT locus. 13,[43][44][45] Relying on these data, we hypothesized that FHIT plays a role in mediating the cellular response to cigarette smoke. To test this, siRNA-treated HBEC3-TK cells were exposed to 1% CSE for 4 hours prior to RNA extraction and microarray analysis.…”

Section: Gene Expression Changes In Response To Fhit Knockdownmentioning

confidence: 99%

“…1,[4][5][6][7][8][9][10][11] Tumors expressing loss of FHIT are typically of epithelial origin, and FHIT has been shown to be a common target of carcinogens, particularly cigarette smoke. [12][13][14][15] Exposure to cigarette smoke is associated with FHIT exon deletion and translocation, as well as hypermethylation of the FHIT promoter with consequent loss of Fhit protein and development of malignancy. 5,9,16,17 Previous work clearly demonstrates the tumor suppressor activity of FHIT.…”

Section: Introductionmentioning

confidence: 99%

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A knockdown with smoke model reveals FHIT as a repressor of Heme oxygenase 1

Boylston

Brenner²

2014

Cell Cycle

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Fragile histidine triad (FHIT) gene deletions are among the earliest and most frequent events in carcinogenesis, particularly in carcinogen-exposed tissues. Though FHIT has been established as an authentic tumor suppressor, the mechanism underlying tumor suppression remains opaque. Most experiments designed to clarify FHIT function have analyzed the consequence of re-expressing FHIT in FHIT-negative cells. However, carcinogenesis occurs in cells that transition from FHIT-positive to FHIT-negative. To better understand cancer development, we induced FHIT loss in human bronchial epithelial cells with RNA interference. Because FHIT is a demonstrated target of carcinogens in cigarette smoke, we combined FHIT silencing with cigarette smoke extract (CSE) exposure and measured gene expression consequences by RNA microarray. The data indicate that FHIT loss enhances the expression of a set of oxidative stress response genes after exposure to CSE, including the cytoprotective enzyme heme oxygenase 1 (HMOX1) at the RNA and protein levels. Data are consistent with a mechanism in which Fhit protein is required for accumulation of the transcriptional repressor of HMOX1, Bach1 protein. We posit that by allowing superinduction of oxidative stress response genes, loss of FHIT creates a survival advantage that promotes carcinogenesis.

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Chromosomal Instability in Amniocytes From Fetuses of Mothers Who Smoke

Chica

Ribas²,

Giraldo³

et al. 2005

JAMA

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Context Tobacco increases the risk of systemic diseases, and it has adverse effects on pregnancy. However, only indirect data have been published on a possible genotoxic effect on pregnancy in humans. Objectives To determine whether maternal smoking has a genotoxic effect on amniotic cells, expressed as an increased chromosomal instability, and to analyze whether any chromosomal regions are especially affected by exposure to tobacco. Design, Setting, and Patients In this prospective study, amniocytes were obtained by routine amniocentesis for prenatal diagnosis from 25 controls and 25 women who smoke (Ն10 cigarettes/d for Ն10 years), who were asked to fill out a smoking questionnaire concerning their smoking habits. Chromosomal instability was analyzed in blinded fashion by 2 independent observers in routine chromosome spreads. Breakpoints implicated in chromosomal abnormalities were identified by G-banding. Main Outcome Measures Association between maternal smoking and increased chromosomal instability in amniotic fluid cells, expressed as chromosomal lesions (gaps and breaks) and structural chromosomal abnormalities. Results Comparison of cytogenetic data between smokers and nonsmokers (controls) showed important differences for the proportion of structural chromosomal abnormalities (smokers: 12.1% [96/793]; controls: 3.5% [26/752]; P=.002) and to a lesser degree for the proportion of metaphases with chromosomal instability (smok

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Direct correlation between FRA3B expression and cigarette smoking

Cited by 62 publications

References 40 publications

Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias

Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias

A knockdown with smoke model reveals FHIT as a repressor of Heme oxygenase 1

Chromosomal Instability in Amniocytes From Fetuses of Mothers Who Smoke

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