Promising molecular targets for cancer prevention: AP-1, NF-κB and Pdcd4

Abstract There are still many unanswered questions regarding the processes by which extracellular signals are transduced from plasma-membrane receptors to the transcription machinery in the nucleus and the translation machinery in the cytoplasm. Some of these gene expression events become misregulated as a result of environmental or endogenous exposure to agents that cause multistage carcinogenesis. We are now beginning to identify and validate the crucial molecular events that drive the rate-limiting steps of carcinogenesis and to target these events for cancer prevention. Transcription factors AP-1 and nuclear factor κB can be specifically targeted to prevent cancer induction in mouse models. A protein known as programmed-cell-death-4 is a new potential molecular target that has a surprising mode of action.

[1]  B. Ozanne,et al.  AP-1-mediated invasion requires increased expression of the hyaluronan receptor CD44 , 1997, Molecular and cellular biology.

[2]  T. Honjo,et al.  Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death. , 1995, Gene.

[3]  B. Spiegelman,et al.  Common DNA binding site for Fos protein complexesand transcription factor AP-1 , 1988, Cell.

[4]  M. Karin,et al.  Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor , 1987, Cell.

[5]  T. Kerppola,et al.  Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity , 2001, Oncogene.

[6]  N. Colburn,et al.  Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  T. Curran,et al.  Structure of the FBJ murine osteosarcoma virus genome: molecular cloning of its associated helper virus and the cellular homolog of the v-fos gene from mouse and human cells , 1983, Molecular and cellular biology.

[8]  P. Vogt,et al.  v-jun encodes a nuclear protein with enhancer binding properties of AP-1 , 1988, Cell.

[9]  R. Tjian,et al.  Fos-associated protein p39 is the product of the jun proto-oncogene. , 1988, Science.

[10]  J. Minna,et al.  Deregulated expression of human c-jun transforms primary rat embryo cells in cooperation with an activated c-Ha-ras gene and transforms rat-1a cells as a single gene. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[11]  N. Colburn,et al.  Tumor promoter-induced ornithine decarboxylase gene expression occurs independently of AP-1 activation , 1999, Oncogene.

[12]  N. Colburn,et al.  Transactivation of Fra-1 and Consequent Activation of AP-1 Occur Extracellular Signal-Regulated Kinase Dependently , 2002, Molecular and Cellular Biology.

[13]  E. Duysen,et al.  Inhibition of phorbol ester-induced AP-1-DNA binding, c-Jun protein and c-jun mRNA by dietary energy restriction is reversed by adrenalectomy in SENCAR mouse epidermis. , 2001, Carcinogenesis.

[14]  N. Colburn,et al.  AP1/jun function is differentially induced in promotion-sensitive and resistant JB6 cells. , 1989, Science.

[15]  M. Santoro,et al.  Thyroid cell transformation requires the expression of the HMGA1 proteins , 2002, Oncogene.

[16]  Z. Dong,et al.  Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  L. Foulds.  Multiple etiologic factors in neoplastic development. , 1965, Cancer research.

[18]  D. S. St. Clair,et al.  Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. , 2001, Cancer research.

[19]  N. Colburn,et al.  A dominant negative c-jun specifically blocks okadaic acid-induced skin tumor promotion. , 2002, Cancer research.

[20]  Weiqun Wang,et al.  Adrenalectomy abrogates reduction of 12-O-tetradecanoylphorbol-13-acetate-induced extracellular signal-regulated protein kinase activity in the epidermis of dietary energy-restricted SENCAR mice: implications of glucocorticoid hormone. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[21]  Michael Karin,et al.  NF-κB in cancer: from innocent bystander to major culprit , 2002, Nature Reviews Cancer.

[22]  E. Wagner,et al.  AP-1 in mouse development and tumorigenesis , 2001, Oncogene.

[23]  G. Kollias,et al.  Mice deficient in tumor necrosis factor-α are resistant to skin carcinogenesis , 1999, Nature Medicine.

[24]  G. Viglietto,et al.  Neoplastic transformation of rat thyroid cells requires the junB and fra‐1 gene induction which is dependent on the HMGI‐C gene product , 1997, The EMBO journal.

[25]  A. Porter,et al.  Neuronal Differentiation and Protection from Nitric Oxide-Induced Apoptosis Require c-Jun-Dependent Expression of NCAM140 , 2002, Molecular and Cellular Biology.

[26]  N. Colburn,et al.  Protection against human papillomavirus type 16‐E7 oncogene‐induced tumorigenesis by in vivo expression of dominant‐negative c‐jun † , 2002, Molecular carcinogenesis.

[27]  N. Colburn,et al.  A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-κB or ODC transactivation , 2001, Oncogene.

[28]  N. Colburn,et al.  Induced expression of dominant‐negative c‐jun downregulates NFκB and AP‐1 target genes and suppresses tumor phenotype in human keratinocytes , 2000, Molecular carcinogenesis.

[29]  T. Hunter,et al.  The c-fos protein interacts with c-Jun AP-1 to stimulate transcription of AP-1 responsive genes , 1988, Cell.

[30]  A. Bode,et al.  Deficiency of c-Jun-NH(2)-terminal kinase-1 in mice enhances skin tumor development by 12-O-tetradecanoylphorbol-13-acetate. , 2002, Cancer research.

[31]  K. Anderson,et al.  Identification of genes regulated by Dexamethasone in multiple myeloma cells using oligonucleotide arrays , 2002, Oncogene.

[32]  E. Goldsmith,et al.  A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation , 1998, Current Biology.

[33]  T. Hunter,et al.  Oncogene jun encodes a sequence-specific trans- activator similar to AP-1 , 1988, Nature.

[34]  J. Hoidal,et al.  An NAD(P)H oxidase regulates growth and transcription in melanoma cells. , 2002, American journal of physiology. Cell physiology.

[35]  V. Berezin,et al.  Fra-1 Induces Morphological Transformation and Increases In Vitro Invasiveness and Motility of Epithelioid Adenocarcinoma Cells , 1998, Molecular and Cellular Biology.

[36]  N. Colburn,et al.  Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Busslinger,et al.  Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron , 1995, Molecular and cellular biology.

[38]  W. Park,et al.  Up-regulation of PDCD4 in senescent human diploid fibroblasts. , 2002, Biochemical and biophysical research communications.

[39]  V. M. Pain.  Initiation of protein synthesis in eukaryotic cells. , 1996, European journal of biochemistry.

[40]  N. Colburn,et al.  Molecular targets for cancer prevention: a meeting review of the third American Cancer Society-Schilling Research Conference. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[41]  P. Maliakal,et al.  Inhibition of carcinogenesis by tea. , 1997, Nature.

[42]  Weiya Ma,et al.  Shortage of mitogen-activated protein kinase is responsible for resistance to AP-1 transactivation and transformation in mouse JB6 cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[43]  R. DuBois,et al.  Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor , 2001, Oncogene.

[44]  A. Bode,et al.  Signal transduction pathways: targets for chemoprevention of skin cancer. , 2000, The Lancet. Oncology.

[45]  N. Colburn,et al.  The role of AP-1, NF-κB and ROS/NOS in skin carcinogenesis: The JB6 model is predictive , 2004, Molecular and Cellular Biochemistry.

[46]  B. Spiegelman,et al.  c-fos is required for malignant progression of skin tumors , 1995, Cell.

[47]  R. Tjian,et al.  Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. , 1987, Science.

[48]  R. Orlowski,et al.  NF-?B as a therapeutic target in cancer , 2002 .

[49]  R. Lotan,et al.  Retinoids and their receptors in cancer development and chemoprevention. , 2002, Critical reviews in oncology/hematology.

[50]  Constance E. Brinckerhoff,et al.  Matrix metalloproteinases: a tail of a frog that became a prince , 2002, Nature Reviews Molecular Cell Biology.

[51]  B. Franza,et al.  Fos and jun: The AP-1 connection , 1988, Cell.

[52]  M. Birrer,et al.  Stable expression of a c-JUN deletion mutant in two malignant mouse epidermal cell lines blocks tumor formation in nude mice. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[53]  N. Colburn,et al.  Activator protein 1 (AP-1)– and nuclear factor κB (NF-κB)–dependent transcriptional events in carcinogenesis , 2000 .

[54]  N. Colburn,et al.  Expression of dominant negative Jun inhibits elevated AP-1 and NF-κB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes , 1998, Oncogene.

[55]  M. Yaniv,et al.  Transformation by ras modifies AP1 composition and activity , 1997, Oncogene.

[56]  M. Birrer,et al.  Suppression of oncogene-induced transformation by a deletion mutant of c-jun. , 1993, Oncogene.