Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25

Wan, Minghong; Vyas, Rakesh Kumar; Zheng, Jianping; Granada, Eileen; Dubeau, Louis

doi:10.1038/sj.onc.1202476

Cited by 39 publications

(24 citation statements)

References 31 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LOT1 is localized at human chromosome 6q24-25, a chromosomal region known to harbor a tumor suppressor gene for several types of neoplasia (Wan et al, 1999). Analysis of allelic deletion in the tumor tissues provided additional evidence supporting the LOT1 0 s potential role in the pathogenesis of ovarian and breast cancer and possibly in other types of cancer.…”

Section: Chromosomal Deletion and Rearrangementmentioning

confidence: 94%

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Abdollahi

2006

Journal Cellular Physiology

View full text Add to dashboard Cite

Lost-on-transformation 1 (LOT1) (PLAGL1/ZAC1) is a member of the novel subfamily of zinc-finger transcription factors, designated as PLAG family. The other members in this group include PLAG1 and PLAGL2, which share high homology with each other and with LOT1, particularly in their zinc-finger amino-terminal region. They are structurally similar but functionally different. For example, the LOT1 gene encodes a growth suppressor protein and is localized on human chromosome 6q24-25, a chromosomal region that is frequently deleted in many types of human cancers. The gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus (TNDM). LOT1 is a target of growth factor signaling pathway(s) and silenced by epigenetic mechanisms, as well as by the loss of heterozygosity in different tumor tissues. PLAG1 is a protooncogene that is localized on chromosome 8q12 and was found to be a target of several types of chromosomal rearrangement including the one identified in pleomorphic adenomas of the salivary gland. Since the discovery of the PLAG family members in 1997, much has been learned about their structure and function, as are summarized in this review. While the available data suggest that these proteins may play important roles in regulating normal physiological functions in the mammals, a great deal more about their signaling pathway(s), potential role in the complex pathologies such as cancer and developmental disorders, and functional relationship between different family members and splice variants still remains to be uncovered.

show abstract

Section: Chromosomal Deletion and Rearrangementmentioning

confidence: 94%

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Abdollahi

2006

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Several functional studies further substantiated the presence of chromosome 6 tumor suppressor gene(s). For example, introduction of a normal human chromosome 6 by microcell-mediated chromosome transfer techniques into several types of tumor cells, including malignant melanoma (Trent et al, 1990;Negrini et al, 1994;Welch et al, 1994), ovarian cancer (Wan et al, 1999), breast cancer (Theile et al, 1996) and uterine endometrial carcinoma (Yamada et al, 1990), resulted in inhibition of tumor cell growth and a reversal of the tumorigenic potential of these cells in nude mice.…”

Section: Introductionmentioning

confidence: 99%

UTRN on chromosome 6q24 is mutated in multiple tumors

Huang

Zhao

et al. 2007

Oncogene

View full text Add to dashboard Cite

“…The A-kinase anchoring protein 12 (AKAP12; also known as Gravin, and its rodent orthologue src-suppressed C-kinase substrate, SSeCKS), a multivalent anchoring protein and an important regulator of the h2-adrenergic receptor complex, controls cell signaling, cell adhesion, mitogenesis and differentiation, and possesses tumor suppressor activity (1)(2)(3)(4)(5). The AKAP12 gene maps to chromosome 6q24-25.2, a locus that frequently contains deletions in human cancers (2,(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of theAKAP12Promoter is a Biomarker of Barrett's-Associated Esophageal Neoplastic Progression

Jin

Hamilton

Yang

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

The A-kinase anchoring protein 12 (AKAP12) is a kinase scaffold protein with known tumor suppressor activity. Recently, AKAP12 promoter hypermethylation was reported in gastric and colorectal cancers. We examined AKAP12 promoter hypermethylation using real-time methylation-specific PCR in 259 human esophageal tissues. AKAP12 hypermethylation showed highly discriminative receiver-operator characteristic (ROC) curve profiles, clearly distinguishing esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma and normal esophagus (P < 0.0001). AKAP12-normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's, and EAC than in normal esophagus (P < 0.0000001). AKAP12 hypermethylation frequency was zero in normal esophagus but increased early during neoplastic progression, to 38.9% in BE from patients with Barrett's alone, 52.5% in dysplastic Barrett's metaplasia, and 52.2% in EAC. AKAP12 hypermethylation levels were significantly higher in normal esophageal epithelia from patients with EAC (mean = 0.00082) than in normal esophagi from patients without Barrett's or esophageal cancer (mean = 0.00007; P = 0.006). There was a significant correlation between AKAP12 hypermethylation and BE segment length, a known clinical neoplastic progression risk factor. In contrast, only 2 (7.7%) of 26 esophageal squamous cell carcinomas exhibited AKAP12 hypermethylation. Treatment of BIC and OE33 EAC cells with 5-aza-2'-deoxycytidine reduced AKAP12 methylation and increased AKAP12 mRNA expression. AKAP12 mRNA levels in EACs with unmethylated AKAP12 (mean = 0.1663) were higher than in EACs with methylated AKAP12 (mean = 0.0668). We conclude that promoter hypermethylation of AKAP12 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker for the early detection of EAC.

show abstract

Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25

Cited by 39 publications

References 31 publications

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

UTRN on chromosome 6q24 is mutated in multiple tumors

Hypermethylation of theAKAP12Promoter is a Biomarker of Barrett's-Associated Esophageal Neoplastic Progression

Contact Info

Product

Resources

About