BHLHB3: a candidate tumor suppressor in lung cancer

Falvella, Felicia Stefania; Colombo, Francesca; Spinola, Monica; Campiglio, Manuela; Pastorino, Ugo; Dragani, Tommaso A.

doi:10.1038/sj.onc.1211038

Cited by 17 publications

(17 citation statements)

References 12 publications

(17 reference statements)

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“…BHLHB3 is a clock gene (19, 20), a transcriptional repressor (18) and importantly a tumor suppressor in lung cancer (21). In D-HEp3 cells BHLHB3 is induced by p38 and was positively linked to genes involved in extracellular matrix biology (e.g., collagen-I α1, MMP2) (Fig1B).…”

Section: Resultsmentioning

confidence: 99%

Computational Identification of a p38SAPK-Regulated Transcription Factor Network Required for Tumor Cell Quiescence

et al. 2009

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The stress-activated kinase p38 plays key roles in tumor suppression and induction of tumor cell dormancy. However, the mechanisms behind these functions remain poorly understood. Using computational tools, we identified a transcription factor (TF) network regulated by p38A/B and required for human squamous carcinoma cell quiescence in vivo. We found that p38 transcriptionally regulates a core network of 46 genes that includes 16 TFs. Activation of p38 induced the expression of the TFs p53 and BHLHB3, while inhibiting c-Jun and FoxM1 expression. Furthermore, induction of p53 by p38 was dependent on c-Jun down-regulation. Accordingly, RNAi down-regulation of BHLHB3 or p53 interrupted tumor cell quiescence, while down-regulation of c-Jun or FoxM1 or overexpression of BHLHB3 in malignant cells mimicked the onset of quiescence. Our results identify components of the regulatory mechanisms driving p38-induced cancer cell quiescence. These may regulate dormancy of residual disease that usually precedes the onset of metastasis in many cancers.

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Section: Resultsmentioning

confidence: 99%

Computational Identification of a p38SAPK-Regulated Transcription Factor Network Required for Tumor Cell Quiescence

et al. 2009

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“…2) were proposed, of which includes SRY-box5 (SOX5). [18][19][20][21][22][23][24][25][26][27][28][29] Based on the argument that chromosome 12p12.1 is a frequently altered chromosomal site in prostate cancer and the fact that SOX5 has recently been shown to play a role in several cancer types, including those of testicular, skin, brain, lymph node and nasopharyngeal [19][20][21][22][23] ; the authors decided that further work for this study would be focused on the SOX5 gene. However, it should be stressed that studies on other candidate genes in other identified frequently altered chromosomal regions are also currently underway in our laboratory.…”

Section: Smal-pcr Dna Fingerprints Of Matched Microdissected Normal mentioning

confidence: 99%

DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer

Chan

Woolcock

et al. 2009

Intl Journal of Cancer

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Identification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high-grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR-based technique called scanning of microdissected archival lesion (SMAL)-PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31. 3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y-box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL-PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis.

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“…Of the genes that were not included in the pathway illustrated in Figure 2B, BHLHB3 is implicated as a tumor suppressor in lung cancer [54], and TCF8 expression has been inversely correlated with E-cadherin expression in several cancers [55]. EFCAB3, PGBD5, and TOX2 remain to be defined in the context of tumorigenesis.…”

Section: Resultsmentioning

confidence: 99%

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

et al. 2014

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Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression.Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 ‘hits’ that contribute to ccRCC cell proliferation.Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC.

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BHLHB3: a candidate tumor suppressor in lung cancer

Cited by 17 publications

References 12 publications

Computational Identification of a p38SAPK-Regulated Transcription Factor Network Required for Tumor Cell Quiescence

Computational Identification of a p38SAPK-Regulated Transcription Factor Network Required for Tumor Cell Quiescence

DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

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