- Open Access
RNA polymerase III transcription in cancer: the BRF2 connection
© Cabarcas and Schramm; licensee BioMed Central Ltd. 2011
Received: 13 December 2010
Accepted: 25 April 2011
Published: 25 April 2011
RNA polymerase (pol) III transcription is responsible for the transcription of small, untranslated RNAs involved in fundamental metabolic processes such mRNA processing (U6 snRNA) and translation (tRNAs). RNA pol III transcription contributes to the regulation of the biosynthetic capacity of a cell and a direct link exists between cancer cell proliferation and deregulation of RNA pol III transcription. Accurate transcription by RNA pol III requires TFIIIB, a known target of regulation by oncogenes and tumor suppressors. There have been significant advances in our understanding of how TFIIIB-mediated transcription is deregulated in a variety of cancers. Recently, BRF2, a component of TFIIIB required for gene external RNA pol III transcription, was identified as an oncogene in squamous cell carcinomas of the lung through integrative genomic analysis. In this review, we focus on recent advances demonstrating how BRF2-TFIIIB mediated transcription is regulated by tumor suppressors and oncogenes. Additionally, we present novel data further confirming the role of BRF2 as an oncogene, extracted from the Oncomine database, a cancer microarray database containing datasets derived from patient samples, providing evidence that BRF2 has the potential to be used as a biomarker for patients at risk for metastasis. This data further supports the idea that BRF2 may serve as a potential therapeutic target in a variety of cancers.
Cancer is a major health problem afflicting millions of Americans annually and despite tremendous research and treatment advances, is still the leading cause of death amongst men and women younger than age 85 years . A dominant characteristic of many types of cancer cells is its ability to proliferate uncontrollably. RNA polymerase (pol) III contains the largest number of subunits (17 subunits) and is responsible for the transcription of small, less than 300 nucleotides, untranslated RNAs involved in fundamental metabolic processes, such as RNA processing (U6 snRNA) and translation (tRNAs), which contribute to cell proliferation . Thus, deregulation of RNA pol III transcription can lead to aberrant production of critical RNAs contributing to uncontrolled cell growth, a hallmark trait of many types of cancer.
BRF2 (TFIIB-r elated f actor 2) shares structural features with TFIIB and BRF1 (Figure 1B). TFIIB, BRF1 and BRF2 all contain N-terminal zinc ribbon domains, core domains containing imperfect repeats; BRF1 and BRF2 have unrelated C-terminal extensions (Figure 1B) . The C-terminus of BRF2 is required for association with TBP and SNAPc (small nuclear activating protein complex) on the U6 promoter .
RNA pol III and cancer
Many different transformed cell types have been shown to have increased products of RNA pol III, when transformed by DNA tumor viruses, as well as chemical carcinogens [7–11] and their relevance has been validated in tumors of the breast, cervix, esophagus, lung, ovary, parotid, and tongue, but not in corresponding normal tissues tumors . Specifically, RT-PCR analysis has demonstrated that tRNAs are overproduced consistently in human ovarian cancers . Also, tRNA levels have been shown to be 10-fold higher in breast cancer cells than in normal cells . These increases are not simply a consequence of rapid cell proliferation in cancer , but instead contribute to tumorigenesis, as it has been demonstrated that overexpression of tRNAiMet induces proliferation and immortalization of fibroblasts .
Activation of TFIIIB activity has been noted in a variety of cancers types. Increased TBP expression has been observed in a clinically significant number of human colon cancers . Also, overexpression of BRF1 has also been shown to transform mouse embryo fibroblasts . Bdp1 is overexpressed in cells transformed by papovaviruses , but changes in expression levels in specific human cancer types have not been determined. Amplification of BRF2 has been noted in breast cancer [18, 19] and more recently a human bladder cancer cell line . Recently, Lockwood et al. demonstrated that genetic activation of BRF2 represents a unique mechanism of squamous cell carcinoma tumorigenesis, also providing the first clinical evidence implicating BRF2 as a novel lineage-specific oncogene in lung squamous cell carcinoma . This review will focus on BRF2-TFIIIB activity in cancer.
Regulation of BRF2-TFIIIB activity by oncogenes and tumor suppressors
RNA pol III transcription is tightly regulated during the cell cycle to ensure normal cellular growth . Cellular levels of RNA pol III are specifically increased in tissues isolated from mice with myeloma compared to tumor-free mice , directly linking RNA pol III activity and cancer. Recently, it was demonstrated that BRF1 and TBP are capable of driving oncogenic transformation [16, 23]. These observations demonstrate that elevation of RNA pol III transcription contributes to oncogenesis. TFIIIB activity is strictly regulated by Maf1 [24–27], chemopreventative agents , and oncogenes and tumor suppressors which are discussed below.
RB controls cell growth by preventing cell cycle entry in the absence of appropriate mitogenic signals and inactivation is associated with a variety of human cancers . RB regulates RNA pol III transcription by disrupting interactions between TFIIIB and RNA pol III [38, 46–49] RB-mediated repression of U6 transcription can be restored by recombinant SNAPc and TBP .
p53 is activated in response to cellular stress, inducing cell cycle arrest or apoptosis, and its inactivation is considered a critical step in carcinogenesis . p53 represses not only Alu and U6 transcription, but also tRNA, 5S rRNA, VAI, B2 and EBER (Epstein-Barr virus) transcription, establishing p53 as a general repressor of RNA pol III transcription . p53 regulates U6 transcription through interaction with the BRF2-TFIIIB subunit TBP  and SNAPc .
BRCA1 plays a role in DNA repair, cell cycle regulation, apoptosis, genome integrity and ubiquitination [52, 53]. Recently, BRCA1 has been characterized as a general repressor of RNA pol III transcription . BRF2 overexpression alleviates BRCA1 mediated repression of U6 transcription , suggesting that regulation of U6 transcription by BRCA1 occurs, in part, through BRF2. However, it is currently unclear whether the observed inhibition of RNA pol III transcription is a result of direct or indirect interactions between BRCA1 and BRF2, or BRCA1 and TFIIIB in general.
BRF2, a general oncogene?
It is established that RNA pol III is often deregulated in cancers [33–35] and specific elevation of RNA pol III transcripts and RNA pol III transcription factors such as U6 snRNA and BRF2 is a feature of both transformed cells and cancers . Recently, Lockwood et al identified BRF2 as a novel oncogene in lung squamous cell carcinoma demonstrating that overexpression of BRF2 can drive expression of RNA pol III transcripts contributing to squamous cell carcinoma tumorigenesis . However, it cannot currently be ruled out that TFIIIB, particularly the BRF2 subunit, could bind and potentially titrate tumor suppressors, thus alleviating some key mechanisms normally keeping TFIIIB activity in check, contributing to oncogenesis. Additionally, no Brf2-dependent pol III transcript has yet been shown to have transforming activity.
RNA pol III is a fundamental determinant of the capacity of a cell to grow and the identification of BRF2 as an oncogene further demonstrates the importance of proper regulation of RNA pol III transcription. Hence, we queried the Oncomine database to systematically assess gene expression levels of BRF2 in a variety of carcinomas. Oncomine is a bioinformatics initiative which collects, standardizes, analyzes, and delivers cancer transcriptome data to the biomedical research community . Rhodes et al. analysis of cancer transcriptome data has identified the genes, pathways, and networks deregulated across 18,000 cancer gene expression microarrays spanning 35 cancer types (for a comprehensive overview of the Oncomine database refer to ). Differential expression analysis is an important feature of the Oncomine resource. A unique feature of the Oncomine database is Oncomine automatically computes differential expression profiles for cancer types and subtypes allowing for simple query for individual gene expression.
Recently, RNA pol III transcription has been the focus of a Phase I and pharmacokinetic study. Hammond-Thelin et al. studied the effects of a novel nucleoside analog inhibitor (TAS-106) of RNA pol I, II and III, in patients with advanced solid malignancies . Previously, TAS-106 has demonstrated antitumor activity in various human cancer models including leukemic, lung, colorectal, stomach, pancreatic, and gastric cancers . The principal objectives of the study were to determine the maximum tolerated dose in patients, characterize the toxicities associated with TAS-106 administration, determine the pharmacokinetics of TAS-106 and study if there was any indication of antitumor activity in patients . Although this study is in its infancy, it's representative of the potential use of RNA pol III inhibitors as a means of pharmacological target for the treatment of cancers.
By elucidating the mechanism(s) by which RNA pol III transcription is both regulated and deregulated, it will be possible to further understand the mechanism(s) by which aberrant activity of the general transcription machinery contributes to cancer development. Deregulation of RNA pol III transcription in cancers coupled with the observation that TFIIIB, specifically BRF2-TFIIIB, is commonly a target of deregulation in a variety of cancers demonstrates that RNA pol III transcription is indeed a key player in tumorigenesis and could serve as a novel target in the development of pharmacological agents.
This work was supported in part by NIH grant 1R15CA133842-01A1 (LS). The authors wish to apologize, due to space restrictions, that not all TFIIIB studies could be mentioned. We thank Dr. Joby Jacob for his assistance with figure preparation.
- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59 (4): 225-49. 10.3322/caac.20006View ArticlePubMedGoogle Scholar
- Schramm L, Hernandez N: Recruitment of RNA polymerase III to its target promoters. Genes Dev. 2002, 16 (20): 2593-620. 10.1101/gad.1018902View ArticlePubMedGoogle Scholar
- Huang Y, Maraia RJ: Comparison of the RNA polymerase III transcription machinery in Schizosaccharomyces pombe, Saccharomyces cerevisiae and human. Nucleic Acids Res. 2001, 29 (13): 2675-90. 10.1093/nar/29.13.2675PubMed CentralView ArticlePubMedGoogle Scholar
- Geiduschek EP, Kassavetis GA: The RNA polymerase III transcription apparatus. J Mol Biol. 2001, 310 (1): 1-26. 10.1006/jmbi.2001.4732View ArticlePubMedGoogle Scholar
- Dieci G, Fiorino G, Castelnuovo M, Teichmann M, Pagano A: The expanding RNA polymerase III transcriptome. Trends Genet. 2007, 23 (12): 614-22. 10.1016/j.tig.2007.09.001View ArticlePubMedGoogle Scholar
- Saxena A, Ma B, Schramm L, Hernandez N: Structure-function analysis of the human TFIIB-related factor II protein reveals an essential role for the C-terminal domain in RNA polymerase III transcription. Mol Cell Biol. 2005, 25 (21): 9406-18. 10.1128/MCB.25.21.9406-9418.2005PubMed CentralView ArticlePubMedGoogle Scholar
- Wang HD, Yuh CH, Dang CV, Johnson DL: The hepatitis B virus X protein increases the cellular level of TATA-binding protein, which mediates transactivation of RNA polymerase III genes. Mol Cell Biol. 1995, 15 (12): 6720-8.PubMed CentralView ArticlePubMedGoogle Scholar
- White RJ, Stott D, Rigby PW: Regulation of RNA polymerase III transcription in response to Simian virus 40 transformation. Embo J. 1990, 9 (11): 3713-21.PubMed CentralPubMedGoogle Scholar
- Gottesfeld JM, Johnson DL, Nyborg JK: Transcriptional activation of RNA polymerase III-dependent genes by the human T-cell leukemia virus type 1 tax protein. Mol Cell Biol. 1996, 16 (4): 1777-85.PubMed CentralView ArticlePubMedGoogle Scholar
- Larminie CG, Sutcliffe JE, Tosh K, Winter AG, Felton-Edkins ZA, White RJ: Activation of RNA polymerase III transcription in cells transformed by simian virus 40. Mol Cell Biol. 1999, 19 (7): 4927-34.PubMed CentralView ArticlePubMedGoogle Scholar
- Felton-Edkins ZA, White RJ: Multiple mechanisms contribute to the activation of RNA polymerase III transcription in cells transformed by papovaviruses. J Biol Chem. 2002, 277 (50): 48182-91. 10.1074/jbc.M201333200View ArticlePubMedGoogle Scholar
- Chen W, Bocker W, Brosius J, Tiedge H: Expression of neural BC200 RNA in human tumours. J Pathol. 1997, 183 (3): 345-51. 10.1002/(SICI)1096-9896(199711)183:3<345::AID-PATH930>3.0.CO;2-8View ArticlePubMedGoogle Scholar
- Winter AG, Sourvinos G, Allison SJ, Tosh K, Scott PH, Spandidos DA, White RJ: RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors. Proc Natl Acad Sci USA. 2000, 97 (23): 12619-24. 10.1073/pnas.230224097PubMed CentralView ArticlePubMedGoogle Scholar
- Pavon-Eternod M, Gomes S, Geslain R, Dai Q, Rosner MR, Pan T: tRNA over-expression in breast cancer and functional consequences. Nucleic Acids Res. 2009, 37 (21): 7268-80. 10.1093/nar/gkp787PubMed CentralView ArticlePubMedGoogle Scholar
- Marshall L, White RJ: Non-coding RNA production by RNA polymerase III is implicated in cancer. Nat Rev Cancer. 2008, 8 (12): 911-4. 10.1038/nrc2539View ArticlePubMedGoogle Scholar
- Marshall L, Kenneth NS, White RJ: Elevated tRNA(iMet) synthesis can drive cell proliferation and oncogenic transformation. Cell. 2008, 133 (1): 78-89. 10.1016/j.cell.2008.02.035View ArticlePubMedGoogle Scholar
- Johnson SA, Dubeau L, Kawalek M, Dervan A, Schonthal AH, Dang CV, Johnson DL: Increased expression of TATA-binding protein, the central transcription factor, can contribute to oncogenesis. Mol Cell Biol. 2003, 23 (9): 3043-51. 10.1128/MCB.23.9.3043-3051.2003PubMed CentralView ArticlePubMedGoogle Scholar
- Melchor L, Garcia MJ, Honrado E, Pole JC, Alvarez S, Edwards PA, Caldas C, Brenton JD, Benitez J: Genomic analysis of the 8p11-12 amplicon in familial breast cancer. Int J Cancer. 2007, 120 (3): 714-7. 10.1002/ijc.22354View ArticlePubMedGoogle Scholar
- Garcia MJ, Pole JC, Chin SF, Teschendorff A, Naderi A, Ozdag H, Vias M, Kranjac T, Subkhankulova T, Paish C, Ellis I, Brenton JD, Edwards PA, Caldas C: A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes. Oncogene. 2005, 24 (33): 5235-45. 10.1038/sj.onc.1208741View ArticlePubMedGoogle Scholar
- Lockwood WW, Chari R, Coe BP, Thu KL, Garnis C, Malloff CA, Campbell J, Williams AC, Hwang D, Zhu CQ, Buys TP, Yee J, English JC, Macaulay C, Tsao MS, Gazdar AF, Minna JD, Lam S, Lam WL: Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma. PLoS Med. 2010, 7 (7): e1000315- 10.1371/journal.pmed.1000315PubMed CentralView ArticlePubMedGoogle Scholar
- Scott PH, Cairns CA, Sutcliffe JE, Alzuherri HM, McLees A, Winter AG, White RJ: Regulation of RNA polymerase III transcription during cell cycle entry. J Biol Chem. 2001, 276 (2): 1005-14. 10.1074/jbc.M005417200View ArticlePubMedGoogle Scholar
- Schwartz LB, Sklar VE, Jaehning JA, Weinmann R, Roeder RG: Isolation and partial characterization of the multiple forms of deoxyribonucleic acid-dependent ribonucleic acid polymerase in the mouse myeloma, MOPC 315. J Biol Chem. 1974, 249 (18): 5889-97.PubMedGoogle Scholar
- Johnson SA, Dubeau L, Johnson DL: Enhanced RNA polymerase III-dependent transcription is required for oncogenic transformation. J Biol Chem. 2008, 283 (28): 19184-91. 10.1074/jbc.M802872200PubMed CentralView ArticlePubMedGoogle Scholar
- Johnson SS, Zhang C, Fromm J, Willis IM, Johnson DL: Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA polymerases. Mol Cell. 2007, 26 (3): 367-79. 10.1016/j.molcel.2007.03.021View ArticlePubMedGoogle Scholar
- Reina JH, Azzouz TN, Hernandez N: Maf1, a New Player in the Regulation of Human RNA Polymerase III Transcription. PLoS ONE. 2006, 1: e134- 10.1371/journal.pone.0000134PubMed CentralView ArticlePubMedGoogle Scholar
- Rollins J, Veras I, Cabarcas S, Willis I, Schramm L: Human Maf1 negatively regulates RNA polymerase III transcription via the TFIIB family members Brf1 and Brf2. Int J Biol Sci. 2007, 3 (5): 292-302.PubMed CentralView ArticlePubMedGoogle Scholar
- Goodfellow SJ, Graham EL, Kantidakis T, Marshall L, Coppins BA, Oficjalska-Pham D, Gerard M, Lefebvre O, White RJ: Regulation of RNA Polymerase III Transcription by Maf1 in Mammalian Cells. J Mol Biol. 2008,Google Scholar
- Jacob J, Cabarcas S, Veras I, Zaveri N, Schramm L: The green tea component EGCG inhibits RNA polymerase III transcription. Biochem Biophys Res Commun. 2007, 360 (4): 778-83. 10.1016/j.bbrc.2007.06.114PubMed CentralView ArticlePubMedGoogle Scholar
- Johnston IM, Allison SJ, Morton JP, Schramm L, Scott PH, White RJ: CK2 forms a stable complex with TFIIIB and activates RNA polymerase III transcription in human cells. Mol Cell Biol. 2002, 22 (11): 3757-68. 10.1128/MCB.22.11.3757-3768.2002PubMed CentralView ArticlePubMedGoogle Scholar
- Felton-Edkins ZA, Kenneth NS, Brown TR, Daly NL, Gomez-Roman N, Grandori C, Eisenman RN, White RJ: Direct regulation of RNA polymerase III transcription by RB, p53 and c-Myc. Cell Cycle. 2003, 2 (3): 181-4.View ArticlePubMedGoogle Scholar
- Marshall L, White RJ: Non-coding RNA production by RNA polymerase III is implicated in cancer. Nat Rev Cancer. 2008,Google Scholar
- Mauger E, Scott PH: Mitogenic stimulation of transcription by RNA polymerase III. Biochem Soc Trans. 2004, 32 (Pt 6): 976-7.View ArticlePubMedGoogle Scholar
- White RJ: RNA polymerase III transcription--a battleground for tumour suppressors and oncogenes. Eur J Cancer. 2004, 40 (1): 21-7. 10.1016/j.ejca.2003.09.027View ArticlePubMedGoogle Scholar
- White RJ: RNA polymerase III transcription and cancer. Oncogene. 2004, 23 (18): 3208-16. 10.1038/sj.onc.1207547View ArticlePubMedGoogle Scholar
- White RJ: RNA polymerases I and III, growth control and cancer. Nat Rev Mol Cell Biol. 2005, 6 (1): 69-78. 10.1038/nrm1551View ArticlePubMedGoogle Scholar
- White RJ: RNA polymerases I and III, non-coding RNAs and cancer. Trends Genet. 2008,Google Scholar
- Morton JP, Kantidakis T, White RJ: RNA polymerase III transcription is repressed in response to the tumour suppressor ARF. Nucleic Acids Res. 2007, 35 (9): 3046-52. 10.1093/nar/gkm208PubMed CentralView ArticlePubMedGoogle Scholar
- Chu WM, Wang Z, Roeder RG, Schmid CW: RNA polymerase III transcription repressed by Rb through its interactions with TFIIIB and TFIIIC2. J Biol Chem. 1997, 272 (23): 14755-61. 10.1074/jbc.272.23.14755View ArticlePubMedGoogle Scholar
- Cairns CA, White RJ: p53 is a general repressor of RNA polymerase III transcription. Embo J. 1998, 17 (11): 3112-23. 10.1093/emboj/17.11.3112PubMed CentralView ArticlePubMedGoogle Scholar
- Chesnokov I, Chu WM, Botchan MR, Schmid CW: p53 inhibits RNA polymerase III-directed transcription in a promoter-dependent manner. Mol Cell Biol. 1996, 16 (12): 7084-8.PubMed CentralView ArticlePubMedGoogle Scholar
- Crighton D, Woiwode A, Zhang C, Mandavia N, Morton JP, Warnock LJ, Milner J, White RJ, Johnson DL: p53 represses RNA polymerase III transcription by targeting TBP and inhibiting promoter occupancy by TFIIIB. Embo J. 2003, 22 (11): 2810-20. 10.1093/emboj/cdg265PubMed CentralView ArticlePubMedGoogle Scholar
- Stein T, Crighton D, Boyle JM, Varley JM, White RJ: RNA polymerase III transcription can be derepressed by oncogenes or mutations that compromise p53 function in tumours and Li-Fraumeni syndrome. Oncogene. 2002, 21 (19): 2961-70. 10.1038/sj.onc.1205372View ArticlePubMedGoogle Scholar
- Stein T, Crighton D, Warnock LJ, Milner J, White RJ: Several regions of p53 are involved in repression of RNA polymerase III transcription. Oncogene. 2002, 21 (36): 5540-7. 10.1038/sj.onc.1205739View ArticlePubMedGoogle Scholar
- Veras I, Rosen EM, Schramm L: Inhibition of RNA Polymerase III Transcription by BRCA1. Journal of Molecular Biology. 2009, 387 (3): 523-531. 10.1016/j.jmb.2009.02.008View ArticlePubMedGoogle Scholar
- Burkhart DL, Sage J: Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cancer. 2008, 8 (9): 671-82. 10.1038/nrc2399View ArticlePubMedGoogle Scholar
- Hirsch HA, Gu L, Henry RW: The retinoblastoma tumor suppressor protein targets distinct general transcription factors to regulate RNA polymerase III gene expression. Mol Cell Biol. 2000, 20 (24): 9182-91. 10.1128/MCB.20.24.9182-9191.2000PubMed CentralView ArticlePubMedGoogle Scholar
- Larminie CG, Cairns CA, Mital R, Martin K, Kouzarides T, Jackson SP, White RJ: Mechanistic analysis of RNA polymerase III regulation by the retinoblastoma protein. Embo J. 1997, 16 (8): 2061-71. 10.1093/emboj/16.8.2061PubMed CentralView ArticlePubMedGoogle Scholar
- Sutcliffe JE, Brown TR, Allison SJ, Scott PH, White RJ: Retinoblastoma protein disrupts interactions required for RNA polymerase III transcription. Mol Cell Biol. 2000, 20 (24): 9192-202. 10.1128/MCB.20.24.9192-9202.2000PubMed CentralView ArticlePubMedGoogle Scholar
- White RJ, Trouche D, Martin K, Jackson SP, Kouzarides T: Repression of RNA polymerase III transcription by the retinoblastoma protein. Nature. 1996, 382 (6586): 88-90. 10.1038/382088a0View ArticlePubMedGoogle Scholar
- Kruse JP, Gu W: Modes of p53 regulation. Cell. 2009, 137 (4): 609-22. 10.1016/j.cell.2009.04.050PubMed CentralView ArticlePubMedGoogle Scholar
- Gridasova AA, Henry RW: The p53 Tumor Suppressor Protein Represses Human snRNA Gene Transcription by RNA Polymerases II and III Independently of Sequence-Specific DNA Binding. Mol Cell Biol. 2005, 25 (8): 3247-3260. 10.1128/MCB.25.8.3247-3260.2005PubMed CentralView ArticlePubMedGoogle Scholar
- Billack B, Monteiro AN: BRCA1 in breast and ovarian cancer predisposition. Cancer Lett. 2005, 227 (1): 1-7. 10.1016/j.canlet.2004.11.006View ArticlePubMedGoogle Scholar
- Deng CX: BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res. 2006, 34 (5): 1416-26. 10.1093/nar/gkl010PubMed CentralView ArticlePubMedGoogle Scholar
- Cabarcas S, Jacob J, Veras I, Schramm L: Differential expression of the TFIIIB subunits Brf1 and Brf2 in cancer cells. BMC Mol Biol. 2008, 9: 74- 10.1186/1471-2199-9-74PubMed CentralView ArticlePubMedGoogle Scholar
- Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, Barrette TR, Anstet MJ, Kincead-Beal C, Kulkarni P, Varambally S, Ghosh D, Chinnaiyan AM: Oncomine 3.0: genes, pathways, and networks in a collection of 18, 000 cancer gene expression profiles. Neoplasia. 2007, 9 (2): 166-80. 10.1593/neo.07112PubMed CentralView ArticlePubMedGoogle Scholar
- Tomlinson GE, Chen TT, Stastny VA, Virmani AK, Spillman MA, Tonk V, Blum JL, Schneider NR, Wistuba II, Shay JW, Minna JD, Gazdar AF: Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier. Cancer Res. 1998, 58 (15): 3237-42.PubMedGoogle Scholar
- Hammond-Thelin LA, Thomas MB, Iwasaki M, Abbruzzese JL, Lassere Y, Meyers CA, Hoff P, de Bono J, Norris J, Matsushita H, Mita A, Rowinsky EK: Phase I and pharmacokinetic study of 3'-C-ethynylcytidine (TAS-106), an inhibitor of RNA polymerase I, II and III, in patients with advanced solid malignancies. Invest New Drugs. 2010, ,Google Scholar
- Talantov D, Mazumder A, Yu JX, Briggs T, Jiang Y, Backus J, Atkins D, Wang Y: Novel genes associated with malignant melanoma but not benign melanocytic lesions. Clin Cancer Res. 2005, 11 (20): 7234-42. 10.1158/1078-0432.CCR-05-0683View ArticlePubMedGoogle Scholar
- Gumz ML, Zou H, Kreinest PA, Childs AC, Belmonte LS, LeGrand SN, Wu KJ, Luxon BA, Sinha M, Parker AS, Sun LZ, Ahlquist DA, Wood CG, Copland JA: Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma. Clin Cancer Res. 2007, 13 (16): 4740-9. 10.1158/1078-0432.CCR-07-0143View ArticlePubMedGoogle Scholar
- D'Errico M, de Rinaldis E, Blasi MF, Viti V, Falchetti M, Calcagnile A, Sera F, Saieva C, Ottini L, Palli D, Palombo F, Giuliani A, Dogliotti E: Genome-wide expression profile of sporadic gastric cancers with microsatellite instability. Eur J Cancer. 2009, 45 (3): 461-9. 10.1016/j.ejca.2008.10.032View ArticlePubMedGoogle Scholar
- Kickhoefer VA, Searles RP, Kedersha NL, Garber ME, Johnson DL, Rome LH: Vault ribonucleoprotein particles from rat and bullfrog contain a related small RNA that is transcribed by RNA polymerase III. J Biol Chem. 1993, 268 (11): 7868-73.PubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.