Deleted in oral cancer‐1 (
            <i>doc‐l),</i>
            a novel oral tumor suppressor gene

Todd, Randy; McBride, Jim; Tsuji, Takanori; Donoff, R. Bruce; Nagai, Maho; Chou, Ming‐Yung; Chiang, Tao; Wong, David T.

doi:10.1096/fasebj.9.13.7557027

Cited by 82 publications

(88 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mutations, though relatively rare, have also been identified in the SMAD genes and other regulators of the TGF-β pathway in primary OSCC tumors and cell lines [75,92,[94][95][96][97]. CDK2AP1 and Deleted in Oral Cancer -1 (DOC-1), this gene was identified by subtractive hybridization from a hamster oral cancer model [98]. CDK2AP1, a novel cell cycle regulator, has been shown to regulate cell cycle by interacting with CDK2 and preventing phosphorylation of pRB, thus rendering pRB active and able to regulate cell cycle [99].…”

Section: Genetic Alteration In Preneoplastic Lesionsmentioning

confidence: 99%

Molecular mechanisms of head and neck cancer

Deshpande

Wong²

2008

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

Background-With a global incidence rank of eight and a significant portion of head and neck malignancies (~90%), oral squamous cell carcinoma (OSCC) poses a major health risk and is one of the leading cause of mortality in developing nations [1]. Distribution of the incidence of OSCC varies across the world with south-central Asia and Africa leading, followed by eastern and central Europe, and to a lesser extent Australia, Japan, and the United States. Over the past few years there has been a drastic increase in the incidence of oral cancer in most parts of the world [2]. In the United States alone, with about 17 new cases/100,000, oral cancer is the fifth most common and sixth leading cause of cancer-related mortality per year [3].While men tend to have a higher incidence of OSCC (6.6/100,000) compared to women (2.9/100,000), there is an equal mortality rate between the sexes (50%).

show abstract

Section: Genetic Alteration In Preneoplastic Lesionsmentioning

confidence: 99%

Molecular mechanisms of head and neck cancer

Deshpande

Wong²

2008

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

show abstract

“…LT-and ST-CR induced the expression of cyclin-dependent kinase 2-associated protein 1 (Cdkap1), a putative tumor-suppressor gene (50). Overexpression of this gene suggests that LT-and ST-CR enhance antiproliferative growth control.…”

Section: St-cr Reproduced the Majority Of The Effects Of Lt-cr On Age-mentioning

confidence: 99%

Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice

Cao

Dhahbi

Mote

et al. 2001

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

385

244

View full text Add to dashboard Cite

We present genome-wide microarray expression analysis of 11,000 genes in an aging potentially mitotic tissue, the liver. This organ has a major impact on health and homeostasis during aging. The effects of life-and health-span-extending caloric restriction (CR) on gene expression among young and old mice and between long-term CR (LT-CR) and short-term CR (ST-CR) were examined. This experimental design allowed us to accurately distinguish the effects of aging from those of CR on gene expression. Aging was accompanied by changes in gene expression associated with increased inflammation, cellular stress, and fibrosis, and reduced capacity for apoptosis, xenobiotic metabolism, normal cell-cycling, and DNA replication. LT-CR and just 4 weeks of ST-CR reversed the majority of these changes. LT-CR produced in young mice a pattern of gene expression that is a subset of the changes found in old LT-CR mice. It is possible that the early changes in gene expression, which extend into old age, are key to the life-and health-span-extending effects of CR. Further, ST-CR substantially shifted the ''normo-aging'' genomic profile of old control mice toward the ''slow-aging'' profile associated with LT-CR. Therefore, many of the genomic effects of CR are established rapidly. Thus, expression profiling should prove useful in quickly identifying CRmimetic drugs and treatments.P ublished microarray studies of mammalian aging have focused on the postmitotic tissues, muscle and brain (1-3). These studies found that aging was associated with changes in gene expression linked to the development of the characteristic age-related pathologies of these tissues. In contrast to muscle and brain, the liver is a potentially mitotic tissue that is thought to age well from a clinical perspective (4). The liver is the central organ for the regulation of glucose homeostasis, xenobiotic metabolism and detoxification, and steroid hormone biosynthesis and degradation. This organ also has a major impact on health and homeostasis through its control of serum protein composition. While differentiated hepatic functions are generally well maintained with age, changes do occur. Serum and biliary cholesterol rise, liver regeneration declines, hepatic drug clearance decreases, and liver volume and blood flow decrease (4). The resilience of the liver to aging, and its central role in the maintenance of whole body health and homeostasis make it an intriguing target for genome-wide expression analysis of aging.Caloric restriction (CR) is the only intervention shown to extend lifespan in mammals (5). It is also the most effective means known of reducing cancer incidence and increasing the mean age of onset of age-related diseases and tumors (6). Our studies made use of an experimental design that allowed us to clearly distinguish the effects of diet from those of age on genome-wide expression patterns. Another distinctive aspect of the study allowed us to resolve changes in gene expression induced directly by CR from those that arise over time as a consequence of ...

show abstract

“…Advances in our understanding of these complementary processes are important to support the development of novel preventative and therapeutic strategies for CRC. Cyclin-dependent kinase 2-associated protein 1 (CDK2-AP1) is a highly conserved gene mapped to chromosome 12q24 (Todd et al, 1995). Originally named Deleted-in-oral-cancer-1 (p12 DOCÀ1 ), CDK2-AP1 was identified and characterized by loss of heterozygosity and decreased expression of its translation product, p12 DOCÀ1 in oral squamous cell carcinoma (Todd et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Cyclin-dependent kinase 2-associated protein 1 (CDK2-AP1) is a highly conserved gene mapped to chromosome 12q24 (Todd et al, 1995). Originally named Deleted-in-oral-cancer-1 (p12 DOCÀ1 ), CDK2-AP1 was identified and characterized by loss of heterozygosity and decreased expression of its translation product, p12 DOCÀ1 in oral squamous cell carcinoma (Todd et al, 1995). CDK2-AP1 is constitutively expressed in normal human tissues and has been shown to interact with multiple cell growth regulatory elements Shintani et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Modulation of CDK2-AP1 (p12DOC−1) expression in human colorectal cancer

et al. 2005

View full text Add to dashboard Cite

We have previously demonstrated an association between microsatellite instability and decreased CDK2-AP1 (p12 DOCÀ1 ) expression in human colorectal cancer (CRC) cell lines. In those same studies, induction of CDK2-AP1 expression promoted both cell cycle arrest and apoptosis. The goals of our present study were to better understand the mechanisms leading to reduced CDK2-AP1 expression in microsatellite unstable (MSI) CRC and to study further the effect of CDK2-AP1 modulation on cell proliferation and apoptosis utilizing RNA interference (RNAi) techniques. We used direct sequencing to screen for mutations of the poly (T)8 microsatellite-like region in the 3 0 end of the CDK2-AP1 gene in 24 CRC cell lines. We then utilized an in vitro human mismatch repair (MMR) recombinant system to assess for correction of the mutation and changes in CDK2-AP1 expression secondary to hMLH1 transfection. We also investigated the effect of CDK2-AP1 modulation in four settings: (1) native CDK2-AP1 absence, (2) endogenous CDK2-AP1 expression, (3) RNAi-induced CDK2-AP1 inhibition and (4) induced CDK2-AP1 over expression. The mutation -del T poly (T)8 -at the 3 0 end of the CDK2-AP1 gene was found in 3/12 (25%) of MSI CRC cell lines, but in none of the microsatellite stable samples (0/12). Interestingly, when wild-type MMR protein -MLH1 -was induced in an in vitro human recombinant system, the del T poly (T)8 mutation was reversed and CDK2-AP1 expression increased. RNAi-mediated CDK2-AP1 inhibition was associated with decreased apoptosis and increased cell proliferation in CDK2-AP1-non deficient CRC cell lines. We conclude that mutations in the microsatellite-like sequence of the CDK2-AP1 gene in MSI CRC are associated with decreased CDK2-AP1 expression. In addition, modulation of CDK2-AP1 expression in human CRC alters cell proliferation and apoptosis.

show abstract

Deleted in oral cancer‐1 ( doc‐l), a novel oral tumor suppressor gene

Cited by 82 publications

References 14 publications

Molecular mechanisms of head and neck cancer

Molecular mechanisms of head and neck cancer

Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice

Modulation of CDK2-AP1 (p12DOC−1) expression in human colorectal cancer

Contact Info

Product

Resources

About