GermlineINI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor

Biegel, Jaclyn A.; Fogelgren, Benjamin; Wainwright, Luanne M.; Zhou, Junying; Bevan, Herbert; Rorke, Lucy B.

doi:10.1002/(sici)1098-2264(200005)28:1<31::aid-gcc4>3.0.co;2-y

Cited by 139 publications

(107 citation statements)

References 16 publications

(10 reference statements)

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…We cannot exclude the possibility that Brm mRNA transport is also attenuated or that Brm mRNA is unstable. For typical tumor suppressor genes, such as p53, Rb, and Ini1, loss of function is usually caused by point mutations in the coding sequence or by deletion of the entire locus (Shimizu et al, 1994;Jia et al, 1997;Biegel et al, 1999). Several other tumor suppressor genes, such as p16(INK4a) and p15(INK4b), are often silenced at the level of transcription (Esteller, 2002).…”

Section: Discussionmentioning

confidence: 99%

The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential

et al. 2005

View full text Add to dashboard Cite

The mammalian SWI/SNF chromatin remodeling complex is composed of more than 10 protein subunits, and plays important roles in epigenetic regulation. Each complex includes a single BRG1 or Brm molecule as the catalytic subunit. We previously reported that loss of Brm, but not BRG1, causes transcriptional gene silencing of murine leukemia virus-based retrovirus vectors. To understand the biological function and biogenesis of Brm protein, we examined seven cell lines derived from various human tumors that do not produce Brm protein. We show here that these Brm-deficient cell lines transcribe the Brm genes efficiently as detected by nuclear run-on transcription assay, whereas Brm mRNA and Brm hnRNA were undetectable by reverse transcription-polymerase chain reaction analysis. These results indicate that expression of Brm is strongly and promptly suppressed at the posttranscriptional level, through processing and transport of the primary transcript or through stability of mature Brm mRNA. This suppression was attenuated by transient treatment of these cell lines with HDAC inhibitors probably through indirect mechanism. Importantly, all of the treated cells showed prolonged induction of Brm expression after the removal of HDAC inhibitors, and acquired the ability to maintain retroviral gene expression. These results indicate that these Brm-deficient human tumor cell lines carry a functional Brm gene. Treatment with HDAC inhibitors or introduction of exogenous Brm into Brm-deficient cell lines significantly reduced the oncogenic potential as assessed by colonyforming activity in soft agar or invasion into collagen gel, indicating that, like BRG1, Brm is involved in tumor suppression.

show abstract

Section: Discussionmentioning

confidence: 99%

The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential

et al. 2005

View full text Add to dashboard Cite

show abstract

“…The RT cell lines (INI1À/À) used in this study are MON (Versteege et al, 1998), G401 (ATCC # CRL-1441) and STM (Biegel et al, 1999). Both 4-HPR (purchased from ONBIO, Ontario, Canada, CAS # 65646-68-6) and 4OH-Tam (Sigma Catalogue # H7904) were reconstituted in 100% ethanol, as a 10 mM solutions.…”

Section: Cell Culture and Materialsmentioning

confidence: 99%

Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors

et al. 2005

View full text Add to dashboard Cite

Rhabdoid tumors (RTs) are aggressive and currently incurable pediatric malignancies. INI1/hSNF5 is a tumor suppressor biallelically inactivated in RTs. Our previous studies have indicated that cyclin D1 is a key downstream target of INI1/hSNF5 and genesis and/or survival of RTs in vivo is critically dependent on the presence of cyclin D1. In this report, we have tested the hypothesis that therapeutic targeting of cyclin D1 is an effective means of treating RTs. We found that RNA interference of cyclin D1 in rhabdoid cells was sufficient to induce G1 arrest and apoptosis. Furthermore, we found that pharmacological intervention with low micromolar concentrations of N-(4-hydroxyphenyl)retinamide (4-HPR), which downmodulates cyclin D1, induced G1 arrest and apoptosis in rhabdoid cell lines. 4-HPR in combination with 4-hydroxy-tamoxifen (4OH-Tam), synergistically inhibited survival as well as anchorage-dependent and -independent growth of rhabdoid cells and caused synergistic induction of cell cycle arrest and apoptosis. 4-HPR and tamoxifen exhibited synergistic growth inhibition of RTs in xenograft models in vivo. The effects of combination of drugs were correlated to the depletion of cyclin D1 levels both in in vitro and in vivo tumor models. These results demonstrate that 4-HPR and tamoxifen are effective chemotherapeutic agents for RTs. We propose that downmodulation of cyclin D1 is a novel and effective therapeutic strategy for RTs.

show abstract

“…LOH has been frequently detected on the long arm of chromosome 22 in a variety of human solid tumors, especially in tumor cells of embryonic-neural-crest origin, including meningiomas (Ueki et al, 1999), astrocytomas (Oskam et al, 2000), schwanomas (Twist et al, 1995) and pheochromocytomas (Shin et al, 1993), but also in thyroid carcinomas (Kitamura et al, 2000), colorectal cancers (Castells et al, 1999), ovarian carcinomas (Englefield et al, 1994), renal rhabdoid tumors (Biegel et al, 2000), gastrointestinal metastatic cancer (Kim et al, 2000), breast cancer (Bryan et al, 2000) and head and neck squamous cell carcinomas from different anatomic sites (Bockmu¨hl et al, 1998). In particular, LOH restricted to the 22q13.31 region has been detected in oral cavity carcinomas (Miyakawa et al, 1998;Poli-Frederico et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Quantitative real-time PCR identifies a critical region of deletion on 22q13 related to prognosis in oral cancer

et al. 2002

View full text Add to dashboard Cite

GermlineINI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor

Cited by 139 publications

References 16 publications

The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential

The Brm gene suppressed at the post-transcriptional level in various human cell lines is inducible by transient HDAC inhibitor treatment, which exhibits antioncogenic potential

Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors

Quantitative real-time PCR identifies a critical region of deletion on 22q13 related to prognosis in oral cancer

Contact Info

Product

Resources

About