Krüppel-like Factors KLF6 and KLF6-SV1 in the Diagnosis and Treatment of Cancer

  • Analisa DiFeo
  • Goutham Narla
  • John A. Martignetti


Beyond their initial identification in prostate cancer, the tumor suppressor KLF6 and its alternatively spliced oncogenic isoform KLF6-SV1 have now been associated with a number of human cancers. Expression patterns of each have been linked to tumor stage, disease recurrence, chemotherapy response and overall survival. Most recently, inhibition of KLF6-SV1 has been shown to increase survival in a pre-clinical model of ovarian cancer. This chapter reviews the basic biology of KLF6 and KLF6-SV1 as it relates to cancer, summarizes the published studies to date, and highlights the scientific rationale for therapeutically targeting KLF6 and KLF6-SV1 as a novel treatment paradigm.


Prostate Cancer Ovarian Cancer PC3M Cell Hereditary Prostate Cancer Ovarian Cancer Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agell L, Hernández S, de Muga S, Lorente JA, Juanpere N, Esgueva R, Serrano S, Gelabert A, Lloreta J. KLF6 and TP53 mutations are a rare event in prostate cancer: distinguishing between Taq polymerase artifacts and true mutations. Mod Pathol. 2008 Dec;21(12):1470–8.PubMedCrossRefGoogle Scholar
  2. Bar-Shira A, Matarasso N, Rosner S, Bercovich D, Matzkin H, Orr-Urtreger A. Mutation screening and association study of the candidate prostate cancer susceptibility genes MSR1, PTEN, and KLF6. Prostate. 2006 Jul 1;66(10):1052–60.PubMedCrossRefGoogle Scholar
  3. Benzeno S, Narla G, Allina J, Cheng GZ, Reeves HL, Banck MS, Odin JA, Diehl JA, Germain D, Friedman SL. Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1. Cancer Res. 2004 Jun 1;64(11):3885–91.PubMedCrossRefGoogle Scholar
  4. Bieker JJ. Kruppel-like factors: three fingers in many pies. J Biol Chem. 276:34355–8; 2001.PubMedCrossRefGoogle Scholar
  5. Black AR, Black JD, Azizkhan-Clifford J. Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol. 188:143–60; 2001.PubMedCrossRefGoogle Scholar
  6. Boyault S, Hérault A, Balabaud C, Zucman-Rossi J. Absence of KLF6 gene mutation in 71 hepa-tocellular carcinomas. Hepatology. 2005 Mar;41(3):681–2.PubMedCrossRefGoogle Scholar
  7. Bureau C, Péron JM, Bouisson M, Danjoux M, Selves J, Bioulac-Sage P, Balabaud C, Torrisani J, Cordelier P, Buscail L, Vinel JP. Expression of the transcription factor Klf6 in cirrhosis, macronodules, and hepatocellular carcinoma. J Gastroenterol Hepatol. 2008 Jan;23(1):78–86.PubMedCrossRefGoogle Scholar
  8. Camacho-Vanegas O, Narla G, Teixeira MS, DiFeo A, Misra A, et al Functional inactivation of the KLF6 tumor suppressor gene by loss of heterozygosity and increased alternative splicing in glioblastoma. Int J Cancer. 2007; 121:1390–5.Google Scholar
  9. Chen C, Hyytinen ER, Sun X, Helin HJ, Koivisto PA, Frierson HF Jr, Vessella RL, Dong JT. Deletion, mutation, and loss of expression of KLF6 in human prostate cancer. Am J Pathol. 2003 Apr;162(4):1349–54.PubMedGoogle Scholar
  10. Chen HK, Liu XQ, Lin J, Chen TY, Feng QS, Zeng YX. Mutation analysis of KLF6 gene in human nasopharyngeal carcinomas. Ai Zheng. 2002 Oct;21(10):1047–50.PubMedGoogle Scholar
  11. Cheng XF, Li D, Zhuang M, Chen ZY, Lu DX, Hattori T. Growth inhibitory effect of Krüppel-like factor 6 on human prostatic carcinoma and renal carcinoma cell lines. Tohoku J Exp Med. 2008 Sep;216(1):35–45.PubMedCrossRefGoogle Scholar
  12. Cho YG, Choi BJ, Kim CJ, Song JW, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS. Genetic alterations of the KLF6 gene in colorectal cancers. APMIS. 2006 Jun;114(6):458–64.PubMedCrossRefGoogle Scholar
  13. Cho YG, Choi BJ, Song JW, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS. Aberrant expression of krUppel-like factor 6 protein in colorectal cancers. World J Gastroenterol. 2006 Apr 14;12(14):2250–3.PubMedGoogle Scholar
  14. Cho YG, Kim CJ, Park CH, Yang YM, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS. Genetic alterations of the KLF6 gene in gastric cancer. Oncogene. 2005 Jun 30;24(28): 4588–90.PubMedCrossRefGoogle Scholar
  15. Cho YG, Lee HS, Song JH, Kim CJ, Park YK, Nam SW, Yoo NJ, Lee JY, Park WS. KLF6 IVS1 -27G/A polymorphism with susceptibility to gastric cancers in Korean. Neoplasma. 2008;55(1):47–50.PubMedGoogle Scholar
  16. Dedrick R, Myers C, Bungay PM et al. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 1978;62:1–11.PubMedGoogle Scholar
  17. DiFeo A, Narla G, Camacho-Vanegas O, Nishio H, Rose SL, Buller RE, Friedman SL, Walsh MJ, Martignetti JA. E-cadherin is a novel transcriptional target of the KLF6 tumor suppressor. Oncogene. 2006 Sep 28;25(44):6026–31.PubMedCrossRefGoogle Scholar
  18. DiFeo A, Narla G, Hirshfeld J, Camacho-Vanegas O, Narla J, Rose SL, Kalir T, Yao S, Levine A, Birrer MJ, Bonome T, Friedman SL, Buller RE, Martignetti JA. Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination. Clin Cancer Res. 2006 Jun 15;12(12):3730–9.PubMedCrossRefGoogle Scholar
  19. DiFeo A, Feld L, Rodriguez E, Wang C, Beer DG, Martignetti JA, Narla G. A functional role for KLF6-SV1 in lung adenocarcinoma prognosis and chemotherapy response. Cancer Res. 2008 Feb 15;68(4):965–70.PubMedCrossRefGoogle Scholar
  20. DiFeo A, Huang F, Leake D, Narla G, Martignetti JA. Inhibition of KLF6-SV1: Exploration of a novel breast cancer target. Abstract, CDMRP Era of Hope Meeting, Baltimore, MD 2008.Google Scholar
  21. Difeo A, Huang F, Sangodkar J, Terzo EA, Leake D, Narla G, Martignetti JA KLF6-SV1 is a novel antiapoptotic protein that targets the BH3-only protein NOXA for degradation and whose inhibition extends survival in an ovarian cancer model. Cancer Res. 2009 Jun 1;69(11):4733–41Google Scholar
  22. Difeo A, Martignetti JA, Narla G. The role of KLF6 and its splice variants in cancer therapy. Drug Resist Updat. In Press.Google Scholar
  23. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001 May 24;411(6836): 494–8.CrossRefGoogle Scholar
  24. Gewirtz AM. On future's doorstep: RNA interference and the pharmacopeia of tomorrow. J Clin Invest. 2007 Dec;117(12):3612–4.PubMedCrossRefGoogle Scholar
  25. Girard L, Zöchbauer-Müller S, Virmani AK, Gazdar AF, Minna JD. Genome-wide allelotyp-ing of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering. Cancer Res. 2000 Sep 1;60(17): 4894–906.Google Scholar
  26. Glinsky GV, Glinskii AB, Stephenson AJ, Hoffman RM, Gerald WL. Gene expression profiling predicts clinical outcome of prostate cancer. J Clin Invest. 2004; 113:913–23.PubMedGoogle Scholar
  27. Guo H, Lin Y, Zhang H, Liu J, Zhang N, Li Y, Kong D, Tang Q, Ma D. Tissue factor pathway inhibitor-2 was repressed by CpG hypermethylation through inhibition of KLF6 binding in highly invasive breast cancer cells. BMC Mol Biol. 2007 Dec 3;8:110.PubMedCrossRefGoogle Scholar
  28. Hartel M, Narla G, Wente MN, Giese NA, Martignoni ME, Martignetti JA, Friess H, Friedman SL. Increased alternative splicing of the KLF6 tumour suppressor gene correlates with prognosis and tumour grade in patients with pancreatic cancer. Eur J Cancer. 2008 Sep;44(13): 1895–903.PubMedCrossRefGoogle Scholar
  29. Hermans KG, van Alewijk DC, Veltman JA, van Weerden W, van Kessel AG, Trapman J. Loss of a small region around the PTEN locus is a major chromosome 10 alteration in prostate cancer xenografts and cell lines. Genes Chromosomes Cancer. 2004 Mar;39(3):171–84.PubMedCrossRefGoogle Scholar
  30. Hirasawa Y, Arai M, Imazeki F, Tada M, Mikata R, Fukai K, Miyazaki M, Ochiai T, Saisho H, Yokosuka O. Methylation status of genes upregulated by demethylating agent 5-aza-2′-deoxycytidine in hepatocellular carcinoma. Oncology. 2006;71(1–2):77–85.PubMedGoogle Scholar
  31. Huang X, Li X, Guo B. KLF6 induces apoptosis in prostate cancer cells through up-regulation of ATF3. J Biol Chem. 2008 Oct 31;283(44):29795–801.PubMedCrossRefGoogle Scholar
  32. Ito G, Uchiyama M, Kondo M, Mori S, Usami N. Maeda O, et al. Kruppel-like factor 6 is frequently down-regulated and induces apoptosis in non-small cell lung cancer cells. Cancer Res 2004;64:3838–43.PubMedCrossRefGoogle Scholar
  33. Ittmann M. Allelic loss on chromosome 10 in prostate adenocarcinoma. Cancer Res. 1996;56(9):2143–7.PubMedGoogle Scholar
  34. Jeng YM, Hsu HC. KLF6, a putative tumor suppressor gene, is mutated in astrocytic gliomas. Int J Cancer. 2003 Jul 10;105(5):625–9.PubMedCrossRefGoogle Scholar
  35. Kettunen E, Anttila S, Seppänen JK, Karjalainen A, Edgren H, Lindström I, Salovaara R, Nissén AM, Salo J, Mattson K, Hollmén J, Knuutila S, Wikman H. Differentially expressed genes in nonsmall cell lung cancer: expression profiling of cancer-related genes in squamous cell lung cancer. Cancer Genet Cytogenet. 2004; 149:98–106.PubMedCrossRefGoogle Scholar
  36. Kimmelman AC, Qiao RF, Narla G, Banno A, Lau N, Bos PD, Nuñez Rodriguez N, Liang BC, Guha A, Martignetti JA, Friedman SL, Chan AM. Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6. Oncogene. 2004 Jun 24;23(29):5077–83.PubMedCrossRefGoogle Scholar
  37. Köhler B, Wolter M, Blaschke B, Reifenberger G. Absence of mutations in the putative tumor suppressor gene KLF6 in glioblastomas and meningiomas. Int J Cancer. 2004 Sep 10;111(4): 644–5.PubMedCrossRefGoogle Scholar
  38. Koivisto PA, Hyytinen ER, Matikainen M, Tammela TL, Ikonen T, Schleutker J. Kruppel-like factor 6 germ-line mutations are infrequent in Finnish hereditary prostate cancer. J Urol. 2004 Aug;172(2):506–7.PubMedCrossRefGoogle Scholar
  39. Koivisto PA, Zhang X, Sallinen SL, Sallinen P, Helin HJ, Dong JT, Van Meir EG, Haapasalo H, Hyytinen ER Absence of KLF6 gene mutations in human astrocytic tumors and cell lines. Int J Cancer. 2004 Sep 10;111(4):642–3Google Scholar
  40. Kovacheva VP, Davison JM, Mellott TJ, Rogers AE, Yang S, O'Brien MJ, Blusztajn JK. Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival. FASEB J. In Press.Google Scholar
  41. Kremer-Tal S, Reeves HL, Narla G, Thung SN, Schwartz M, Difeo A, Katz A, Bruix J, Bioulac-Sage P, Martignetti JA, Friedman SL. Frequent inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) in hepatocellular carcinoma. Hepatology. 2004 Nov;40(5):1047–52.PubMedCrossRefGoogle Scholar
  42. Kremer-Tal S, Narla G, Chen Y, Hod E, DiFeo A, Yea S, Lee JS, Schwartz M, Thung SN, Fiel IM, Banck M, Zimran E, Thorgeirsson SS, Mazzaferro V, Bruix J, Martignetti JA, Llovet JM, Friedman SL. Downregulation of KLF6 is an early event in hepatocarcinogenesis, and stimulates proliferation while reducing differentiation. J Hepatol. 2007 Apr;46(4):645–54.PubMedCrossRefGoogle Scholar
  43. Lam DC, Girard L, Suen WS, Chung LP, Tin VP, Lam WK, Minna JD, Wong MP. Establishment and expression profiling of new lung cancer cell lines from Chinese smokers and lifetime never-smokers. J Thorac Oncol. 2006 Nov;1(9):932–42.PubMedCrossRefGoogle Scholar
  44. Lièvre A, Landi B, Côté JF, Veyrie N, Zucman-Rossi J, Berger A, Laurent-Puig P. Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers. Oncogene. 2005 Nov 3;24(48):7253–6.PubMedCrossRefGoogle Scholar
  45. Macleod K, Mullen P, Sewell J, Rabiasz G, Lawrie S, Miller E, Smyth JF, Langdon SP. Altered ErbB receptor signaling and gene expression in cisplatin-resistant ovarian cancer. Cancer Res. 2005 Aug 1;65(15):6789–800.PubMedCrossRefGoogle Scholar
  46. Miyaki M, Yamaguchi T, Iijima T, Funata N, Mori T. Difference in the role of loss of hetero-zygosity at 10p15 (KLF6 locus) in colorectal carcinogenesis between sporadic and familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer patients. Oncology. 2006;71(1–2):131–5.PubMedCrossRefGoogle Scholar
  47. Montanini L, Bissola L, Finocchiaro G. KLF6 is not the major target of chromosome 10p losses in glioblastomas. Int J Cancer. 2004 Sep 10;111(4):640–1.PubMedCrossRefGoogle Scholar
  48. Mühlbauer KR, Gröne HJ, Ernst T, Gröne E, Tschada R, Hergenhahn M, Hollstein M. Analysis of human prostate cancers and cell lines for mutations in the TP53 and KLF6 tumour suppressor genes. Br J Cancer. 2003 Aug 18;89(4):687–90.PubMedCrossRefGoogle Scholar
  49. Mukai S, Hiyama T, Tanaka S, Yoshihara M, Arihiro K, Chayama K. Involvement of Kruppel-like factor 6 (KLF6) mutation in the development of nonpolypoid colorectal carcinoma. World J Gastroenterol. 2007 Aug 7;13(29):3932–8.PubMedGoogle Scholar
  50. Narla G, Heath KE, Reeves HL, Li D, Giono LE, Kimmelman AC, Glucksman MJ, Narla J, Eng FJ, Chan AM, Ferrari AC, Martignetti JA, Friedman SL. KLF6, a candidate tumor suppressor gene mutated in prostate cancer. Science. 2001 Dec 21;294(5551):2563–6.PubMedCrossRefGoogle Scholar
  51. Narla G, Difeo A, Reeves HL, Schaid DJ, Hirshfeld J, Hod E, Katz A, Isaacs WB, Hebbring S, Komiya A, McDonnell SK, Wiley KE, Jacobsen SJ, Isaacs SD, Walsh PC, Zheng SL, Chang BL, Friedrichsen DM, Stanford JL, Ostrander EA, Chinnaiyan AM, Rubin MA, Xu J, Thibodeau SN, Friedman SL, Martignetti JA. A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk. Cancer Res. 2005 Feb 15;65(4):1213–22.PubMedCrossRefGoogle Scholar
  52. Narla G, DiFeo A, Yao S, Banno A, Hod E, Reeves HL, Qiao RF, Camacho-Vanegas O, Levine A, Kirschenbaum A, Chan AM, Friedman SL, Martignetti JA. Targeted inhibition of the KLF6 splice variant, KLF6 SV1, suppresses prostate cancer cell growth and spread. Cancer Res. 2005 Jul 1;65(13):5761–8.PubMedCrossRefGoogle Scholar
  53. Narla G, Kremer-Tal S, Matsumoto N, Zhao X, Yao S, Kelley K, Tarocchi M, Friedman SL. In vivo regulation of p21 by the Kruppel-like factor 6 tumor-suppressor gene in mouse liver and human hepatocellular carcinoma. Oncogene. 2007 Jun 28;26(30):4428–34.PubMedCrossRefGoogle Scholar
  54. Narla G, DiFeo A, Fernandez Y, Dhanasekaran S, Huang F, Sangodkar J, Hod E, Leake D, Friedman SL, Hall SJ, Chinnaiyan AM, Gerald WL, Rubin MA, Martignetti JA. KLF6-SV1 overexpression accelerates human and mouse prostate cancer progression and metastasis. J Clin Invest. 2008 Aug;118(8):2711–21.PubMedCrossRefGoogle Scholar
  55. Pai SI, Lin YY, Macaes B, Meneshian A, Hung CF, Wu TC. Prospects of RNA interference therapy for cancer. Gene Ther. 2006 Mar;13(6):464–77.PubMedCrossRefGoogle Scholar
  56. Pan XC, Chen Z, Chen F, Chen XH, Zhou C, Yang ZG. Mutations of the tumor suppressor Kruppel-like factor 6 (KLF6) gene in hepatocellular carcinoma and its effect of growth suppression on human hepatocellular carcinoma cell line HepG2. Zhonghua Gan Zang Bing Za Zhi. 2006 Feb;14(2):109–13.PubMedGoogle Scholar
  57. Pan XC, Chen Z, Chen F, Chen XH, Jin HY, Xu XY. Inactivation of the tumor suppressor Krüppel-like factor 6 (KLF6) by mutation or decreased expression in hepatocellular carcinomas. J Zhejiang Univ Sci B. 2006 Oct;7(10):830–6.PubMedCrossRefGoogle Scholar
  58. Pan XC, Chen Z, Ji F, Guo ZS, Chen M, Fu JJ. [Effect of KLF6 and its splice variant KLF6V on proliferation and differentiation of human hepatocellular carcinoma HepG2 cells]. Zhonghua Gan Zang Bing Za Zhi. 2008 Sep;16(9):683–7.PubMedGoogle Scholar
  59. Peng D, Sheta EA, Powell SM, Moskaluk CA, Washington K, Goldknopf IL, El-Rifai W. Alterations in Barrett's-related adenocarcinomas: a proteomic approach. Int J Cancer. 2008 Mar 15;122(6):1303–10.PubMedCrossRefGoogle Scholar
  60. Reeves HL, Narla G, Ogunbiyi O, Haq AI, Katz A, Benzeno S, Hod E, Harpaz N, Goldberg S, Tal-Kremer S, Eng FJ, Arthur MJ, Martignetti JA, Friedman SL. Kruppel-like factor 6 (KLF6) is a tumor-suppressor gene frequently inactivated in colorectal cancer. Gastroenterology. 2004 Apr;126(4):1090–103.PubMedCrossRefGoogle Scholar
  61. Sangodkar J, Shi J, Difeo A, Schwartz R, Bromberg R, Choudhri A, McClinch K, Hatami R, Scheer E, Kremer-Tal S, Martignetti JA, Hui A, Leung WK, Friedman SL, Narla G. Functional role of the KLF6 tumour suppressor gene in gastric cancer. Eur J Cancer. In Press.Google Scholar
  62. Seppälä EH, Autio V, Duggal P, Ikonen T, Stenman UH, Auvinen A, Bailey-Wilson JE, Tammela TL, Schleutker J. KLF6 IVS1 -27G>A variant and the risk of prostate cancer in Finland. Eur Urol. 2007 Oct;52(4):1076–81.PubMedCrossRefGoogle Scholar
  63. Singh D, Febbo PG, Ross K, Jackson DG, Manola J, Ladd C, Tamayo P, Renshaw AA, D'Amico AV, Richie JP, Lander ES, Loda M, Kantoff PW, Golub TR, Sellers WR. Gene expression correlates of clinical prostate cancer behavior. Cancer Cell. 2002 Mar;1(2):203–9.PubMedCrossRefGoogle Scholar
  64. Sirach E, Bureau C, Péron JM, Pradayrol L, Vinel JP, Buscail L, Cordelier P. KLF6 transcription factor protects hepatocellular carcinoma-derived cells from apoptosis. Cell Death Differ. 2007 Jun;14(6):1202–10.PubMedCrossRefGoogle Scholar
  65. Song J, Kim CJ, Cho YG, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS. Genetic and epigenetic alterations of the KLF6 gene in hepatocellular carcinoma. J Gastroenterol Hepatol. 2006 Aug;21(8):1286–9.PubMedCrossRefGoogle Scholar
  66. Spinola M, Leoni VP, Galvan A, Korsching E, Conti B, Pastorino U, Ravagnani F, Columbano A, Skaug V, Haugen A, Dragani TA Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene. Cancer Lett. 2007 Jun 28;251(2):311–6Google Scholar
  67. Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006 Mar 1;66(5):2815–25.PubMedCrossRefGoogle Scholar
  68. Teixeira MS, Camacho-Vanegas O, Fernandez Y, Narla G, DiFeo A, Lee B, Kalir T, Friedman SL, Schlecht NF, Genden EM, Urken M, Brandwein-Gensler M, Martignetti JA. KLF6 allelic loss is associated with tumor recurrence and markedly decreased survival in head and neck squamous cell carcinoma. Int J Cancer. 2007 Nov 1;121(9):1976–83.PubMedCrossRefGoogle Scholar
  69. Trimble EL, Thompson S, Christian MC, Minasian L. Intraperitoneal chemotherapy for women with epithelial ovarian cancer. Oncologist. 2008 13:403–9.PubMedCrossRefGoogle Scholar
  70. Trybus TM, Burgess AC, Wojno KJ, Glover TW, Macoska JA. Distinct areas of allelic loss on chromosomal regions 10p and 10q in human PCa. Cancer Res. 1996;56(10):2263–7.PubMedGoogle Scholar
  71. van Deutekom JC, Janson AA, Ginjaar IB, Frankhuizen WS, Aartsma-Rus A, Bremmer-Bout M, den Dunnen JT, Koop K, van der Kooi AJ, Goemans NM, de Kimpe SJ, Ekhart PF, Venneker EH, Platenburg GJ, Verschuuren JJ, van Ommen GJ. Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med. 2007 Dec 27;357(26):2677–86.PubMedCrossRefGoogle Scholar
  72. Vax VV, Gueorguiev M, Dedov II, Grossman AB, Korbonits M. The Krüppel-like transcription factor 6 gene in sporadic pituitary tumours. Endocr Relat Cancer. 2003 Sep;10(3):397–402.PubMedCrossRefGoogle Scholar
  73. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008 Oct;8(10):755–68.PubMedCrossRefGoogle Scholar
  74. Wang S, Chen X, Zhang W, Qiu F. KLF6mRNA expression in primary hepatocellular carcinoma. J Huazhong Univ Sci Technolog Med Sci. 2004;24(6):585–7.PubMedGoogle Scholar
  75. Wang SP, Chen XP, Qiu FZ. A candidate tumor suppressor gene mutated in primary hepatocellular carcinoma: kruppel-like factor 6. Zhonghua Wai Ke Za Zhi. 2004 Oct 22;42(20):1258–61.PubMedGoogle Scholar
  76. Wang SP, Zhou HJ, Chen XP, Ren GY, Ruan XX, Zhang Y, Zhang RL, Chen J. Loss of expression of Kruppel-like factor 6 in primary hepatocellular carcinoma and hepatoma cell lines. J Exp Clin Cancer Res. 2007 Mar;26(1):117–24.PubMedGoogle Scholar
  77. Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov. 2009 Feb;8(2):129–38.PubMedCrossRefGoogle Scholar
  78. Wikman H, Kettunen E, Seppänen JK, Karjalainen A, Hollmén J, Anttila S, Knuutila S. Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene. 2002 Aug 22;21(37):5804–13.PubMedCrossRefGoogle Scholar
  79. Xu J, Gillanders EM, Isaacs SD, Chang BL, Wiley KE, Zheng SL, Jones M, Gildea D, Riedesel E, Albertus J, Freas-Lutz D, Markey C, Meyers DA, Walsh PC, Trent JM, Isaacs WB. Genome-wide scan for prostate cancer susceptibility genes in the Johns Hopkins hereditary prostate cancer families. Prostate. 2003 Dec 1;57(4):320–5.PubMedCrossRefGoogle Scholar
  80. Yea S, Narla G, Zhao X, Garg R, Tal-Kremer S, Hod E, Villanueva A, Loke J, Tarocchi M, Akita K, Shirasawa S, Sasazuki T, Martignetti JA, Llovet JM, Friedman SL. Ras promotes growth by alternative splicing-mediated inactivation of the KLF6 tumor suppressor in hepatocellular carcinoma. Gastroenterology. 2008;134:1521–31.PubMedCrossRefGoogle Scholar
  81. Yin D, Komatsu N, Miller CW, Chumakov AM, Marschesky A, McKenna R, Black KL, Koeffler HP. KLF6: mutational analysis and effect on cancer cell proliferation. Int J Oncol. 2007 Jan;30(1):65–72.PubMedGoogle Scholar
  82. Zhu H, Lam DC, Han KC, Tin VP, Suen WS, Wang E, Lam WK, Cai WW, Chung LP, Wong MP. High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines. Cancer Lett. 2007 Jan 8;245(1–2):303–14.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • Analisa DiFeo
    • 1
  • Goutham Narla
    • 1
  • John A. Martignetti
    • 1
    • 2
  1. 1.Department of Genetics and Genomic SciencesMount Sinai School of MedicineNew YorkUSA
  2. 2.Department of Oncological SciencesMount Sinai School of MedicineNew YorkUSA

Personalised recommendations