RAMP1 is a direct NKX3.1 target gene up-regulated in prostate cancer that promotes tumorigenesis

American Journal of Pathology

Volumn 183, Issue 3, 2013, Pages 951-963

  Logan, Monica ^a   Anderson, Philip D ^b   Saab, Shahrazad T ^b   Hameed, Omar ^b   Abdulkadir, Sarki A ^b,c  

^a MEHARRY MEDICAL COLLEGE   (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; RECEPTOR ACTIVITY MODIFYING PROTEIN 1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING SITE; CANCER CELL; CARCINOGENESIS; CELL PROLIFERATION; CELL STRAIN LNCAP; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; GENE; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE LOCATION; GENE LOCUS; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; MAP2KI GENE; MOUSE; NKX3.1 GENE; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN DEPLETION; RAMP1 GENE; SIGNAL TRANSDUCTION; UPREGULATION;

ANIMALS; CARCINOGENESIS; CELL LINE, TUMOR; CELL PROLIFERATION; DOWN-REGULATION; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE KNOCKDOWN TECHNIQUES; GENES, NEOPLASM; HOMEODOMAIN PROTEINS; HUMANS; MALE; MAP KINASE SIGNALING SYSTEM; MICE; MICE, NUDE; PROSTATE; PROSTATIC NEOPLASMS; PROTEIN BINDING; RECEPTOR ACTIVITY-MODIFYING PROTEIN 1; TRANSCRIPTION FACTORS; UP-REGULATION;

EID: 84883200980     PISSN: 00029440     EISSN: 15252191     Source Type: Journal    
DOI: 10.1016/j.ajpath.2013.05.021     Document Type: Article

References (77)

1. L.M. McLatchie, N.J. Fraser, M.J. Main, A. Wise, J. Brown, N. Thompson, R. Solari, M.G. Lee, and S.M. Foord RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor Nature 393 1998 333 339
2. T. Bouschet, S. Martin, and J.M. Henley Regulation of calcium-sensing-receptor trafficking and cell-surface expression by GPCRs and RAMPs Trends Pharmacol Sci 29 2008 633 639
3. T. Bouschet, S. Martin, and J.M. Henley Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane J Cell Sci 118 2005 4709 4720
4. A. Christopoulos, G. Christopoulos, M. Morfis, M. Udawela, M. Laburthe, A. Couvineau, K. Kuwasako, N. Tilakaratne, and P.M. Sexton Novel receptor partners and function of receptor activity-modifying proteins J Biol Chem 278 2003 3293 3297
5. D. Wootten, H. Lindmark, M. Kadmiel, H. Willcockson, K.M. Caron, J. Barwell, T. Drmota, and D.R. Poyner Receptor activity modifying proteins (RAMPs) interact with the VPAC2 receptor and CRF1 receptors and modulate their function Br J Pharmacol 168 2013 822 834
6. R. Morimoto, F. Satoh, O. Murakami, T. Hirose, K. Totsune, Y. Imai, Y. Arai, T. Suzuki, H. Sasano, S. Ito, and K. Takahashi Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues J Endocrinol 198 2008 175 183
7. M. Aarhus, O. Bruland, G. Bredholt, H. Lybaek, E.S. Husebye, B.K. Krossnes, C. Vedeler, K. Wester, M. Lund-Johansen, and P.M. Knappskog Microarray analysis reveals down-regulation of the tumour suppressor gene WWOX and up-regulation of the oncogene TYMS in intracranial sporadic meningiomas J Neurooncol 88 2008 251 259
8. T.L. Romanuik, T. Ueda, N. Le, S. Haile, T.M. Yong, T. Thomson, R.L. Vessella, and M.D. Sadar Novel biomarkers for prostate cancer including noncoding transcripts Am J Pathol 175 2009 2264 2276
9. W.W. He, P.J. Sciavolino, J. Wing, M. Augustus, P. Hudson, P.S. Meissner, R.T. Curtis, B.K. Shell, D.G. Bostwick, D.J. Tindall, E.P. Gelmann, C. Abate-Shen, and K.C. Carter A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer Genomics 43 1997 69 77
10. C.J. Bieberich, K. Fujita, W.W. He, and G. Jay Prostate-specific and androgen-dependent expression of a novel homeobox gene J Biol Chem 271 1996 31779 31782
11. R. Bhatia-Gaur, A.A. Donjacour, P.J. Sciavolino, M. Kim, N. Desai, P. Young, C.R. Norton, T. Gridley, R.D. Cardiff, G.R. Cunha, C. Abate-Shen, and M.M. Shen Roles for Nkx3.1 in prostate development and cancer Genes Dev 13 1999 966 977
12. S.A. Abdulkadir, J.A. Magee, T.J. Peters, Z. Kaleem, C.K. Naughton, P.A. Humphrey, and J. Milbrandt Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia Mol Cell Biol 22 2002 1495 1503
13. M.J. Kim, R. Bhatia-Gaur, W.A. Banach-Petrosky, N. Desai, Y. Wang, S.W. Hayward, G.R. Cunha, R.D. Cardiff, M.M. Shen, and C. Abate-Shen Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis Cancer Res 62 2002 2999 3004
14. M. Tanaka, I. Komuro, H. Inagaki, N.A. Jenkins, N.G. Copeland, and S. Izumo Nkx3.1, a murine homolog of Drosophila bagpipe, regulates epithelial ductal branching and proliferation of the prostate and palatine glands Dev Dyn 219 2000 248 260
15. E. Asatiani, W.X. Huang, A. Wang, E. Rodriguez Ortner, L.R. Cavalli, B.R. Haddad, and E.P. Gelmann Deletion, methylation, and expression of the NKX3.1 suppressor gene in primary human prostate cancer Cancer Res 65 2005 1164 1173
16. C.D. Vocke, R.O. Pozzatti, D.G. Bostwick, C.D. Florence, S.B. Jennings, S.E. Strup, P.H. Duray, L.A. Liotta, M.R. Emmert-Buck, and W.M. Linehan Analysis of 99 microdissected prostate carcinomas reveals a high frequency of allelic loss on chromosome 8p12-21 Cancer Res 56 1996 2411 2416
17. C. Bowen, L. Bubendorf, H.J. Voeller, R. Slack, N. Willi, G. Sauter, T.C. Gasser, P. Koivisto, E.E. Lack, J. Kononen, O.P. Kallioniemi, and E.P. Gelmann Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression Cancer Res 60 2000 6111 6115
18. S. Akamatsu, R. Takata, K. Ashikawa, N. Hosono, N. Kamatani, T. Fujioka, O. Ogawa, M. Kubo, Y. Nakamura, and H. Nakagawa A functional variant in NKX3.1 associated with prostate cancer susceptibility down-regulates NKX3.1 expression Hum Mol Genet 19 2010 4265 4272
19. E.P. Gelmann, D.J. Steadman, J. Ma, N. Ahronovitz, H.J. Voeller, S. Swope, M. Abbaszadegan, K.M. Brown, K. Strand, R.B. Hayes, and M.J. Stampfer Occurrence of NKX3.1 C154T polymorphism in men with and without prostate cancer and studies of its effect on protein function Cancer Res 62 2002 2654 2659
20. E.M. Kwon, S.K. Holt, R. Fu, S. Kolb, G. Williams, J.L. Stanford, and E.A. Ostrander Androgen metabolism and JAK/STAT pathway genes and prostate cancer risk Cancer Epidemiol 36 2012 347 353
21. S.L. Zheng, J.H. Ju, B.L. Chang, E. Ortner, J. Sun, S.D. Isaacs, J. Sun, K.E. Wiley, W. Liu, M. Zemedkun, P.C. Walsh, J. Ferretti, J. Gruschus, W.B. Isaacs, E.P. Gelmann, and J. Xu Germ-line mutation of NKX3.1 cosegregates with hereditary prostate cancer and alters the homeodomain structure and function Cancer Res 66 2006 69 77
22. C. Abate-Shen, W.A. Banach-Petrosky, X. Sun, K.D. Economides, N. Desai, J.P. Gregg, A.D. Borowsky, R.D. Cardiff, and M.M. Shen Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases Cancer Res 63 2003 3886 3890
23. M.J. Kim, R.D. Cardiff, N. Desai, W.A. Banach-Petrosky, R. Parsons, M.M. Shen, and C. Abate-Shen Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis Proc Natl Acad Sci U S A 99 2002 2884 2889
24. K. Ellwood-Yen, T.G. Graeber, J. Wongvipat, M.L. Iruela-Arispe, J. Zhang, R. Matusik, G.V. Thomas, and C.L. Sawyers Myc-driven murine prostate cancer shares molecular features with human prostate tumors Cancer Cell 4 2003 223 238
25. T. Iwata, D. Schultz, J. Hicks, G.K. Hubbard, L.N. Mutton, T.L. Lotan, C. Bethel, M.T. Lotz, S. Yegnasubramanian, W.G. Nelson, C.V. Dang, M. Xu, U. Anele, C.M. Koh, C.J. Bieberich, and A.M. De Marzo MYC overexpression induces prostatic intraepithelial neoplasia and loss of Nkx3.1 in mouse luminal epithelial cells PLoS One 5 2010 e9427
26. P.D. Anderson, S.A. McKissic, M. Logan, M. Roh, O.E. Franco, J. Wang, I. Doubinskaia, R. van der Meer, S.W. Hayward, C.M. Eischen, I.E. Eltoum, and S.A. Abdulkadir Nkx3.1 and Myc crossregulate shared target genes in mouse and human prostate tumorigenesis J Clin Invest 122 2012 1907 1919
27. X. Ouyang, T.L. DeWeese, W.G. Nelson, and C. Abate-Shen Loss-of-function of Nkx3.1 promotes increased oxidative damage in prostate carcinogenesis Cancer Res 65 2005 6773 6779
28. J.A. Magee, S.A. Abdulkadir, and J. Milbrandt Haploinsufficiency at the Nkx3.1 locus: a paradigm for stochastic, dosage-sensitive gene regulation during tumor initiation Cancer Cell 3 2003 273 283
29. J. Wang Pim1 kinase is required to maintain tumorigenicity in MYC-expressing prostate cancer cells Oncogene 31 2012 1794 1803
30. X. Wu, M. Zayzafoon, X. Zhang, and O. Hameed Is there a role for fatty acid synthase in the diagnosis of prostatic adenocarcinoma? a comparison with AMACR Am J Clin Pathol 136 2011 239 246
31. D.R. Rhodes, S. Kalyana-Sundaram, V. Mahavisno, R. Varambally, J. Yu, B.B. Briggs, T.R. Barrette, M.J. Anstet, C. Kincead-Beal, P. Kulkarni, S. Varambally, D. Ghosh, and A.M. Chinnaiyan Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles Neoplasia 9 2007 166 180
32. M. Roh, R. van der Meer, and S.A. Abdulkadir Tumorigenic polyploid cells contain elevated ROS and ARE selectively targeted by antioxidant treatment J Cell Physiol 227 2012 801 812
33. M. Roh, B. Gary, C. Song, N. Said-Al-Naief, A. Tousson, A. Kraft, I.E. Eltoum, and S.A. Abdulkadir Overexpression of the oncogenic kinase Pim-1 leads to genomic instability Cancer Res 63 2003 8079 8084
34. M. Roh, C. Song, J. Kim, and S.A. Abdulkadir Chromosomal instability induced by Pim-1 is passage-dependent and associated with dysregulation of cyclin B1 J Biol Chem 280 2005 40568 40577
35. S.A. Abdulkadir, Z. Qu, E. Garabedian, S.K. Song, T.J. Peters, J. Svaren, J.M. Carbone, C.K. Naughton, W.J. Catalona, J.J. Ackerman, J.I. Gordon, P.A. Humphrey, and J. Milbrandt Impaired prostate tumorigenesis in Egr1-deficient mice Nat Med 7 2001 101 107
36. A.P. Mogal, R. van der Meer, P.S. Crooke, and S.A. Abdulkadir Haploinsufficient prostate tumor suppression by Nkx3.1: a role for chromatin accessibility in dosage-sensitive gene regulation J Biol Chem 282 2007 25790 25800
37. J. Kim, M. Roh, and S.A. Abdulkadir Pim1 promotes human prostate cancer cell tumorigenicity and c-MYC transcriptional activity BMC Cancer 10 2010 248
38. E.E. Martinez, P.D. Anderson, M. Logan, and S.A. Abdulkadir Antioxidant treatment promotes prostate epithelial proliferation in nkx3.1 mutant mice PLoS One 7 2012 e46792
39. L. Gautier, L. Cope, B.M. Bolstad, and R.A. Irizarry affy-analysis of Affymetrix GeneChip data at the probe level Bioinformatics 20 2004 307 315
40. R.A. Irizarry, B. Hobbs, F. Collin, Y.D. Beazer-Barclay, K.J. Antonellis, U. Scherf, and T.P. Speed Exploration, normalization, and summaries of high density oligonucleotide array probe level data Biostatistics 4 2003 249 264
41. A. Subramanian, P. Tamayo, V.K. Mootha, S. Mukherjee, B.L. Ebert, M.A. Gillette, A. Paulovich, S.L. Pomeroy, T.R. Golub, E.S. Lander, and J.P. Mesirov Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles Proc Natl Acad Sci U S A 102 2005 15545 15550
42. A.I. Su, J.B. Welsh, L.M. Sapinoso, S.G. Kern, P. Dimitrov, H. Lapp, P.G. Schultz, S.M. Powell, C.A. Moskaluk, H.F. Frierson Jr., and G.M. Hampton Molecular classification of human carcinomas by use of gene expression signatures Cancer Res 61 2001 7388 7393
43. J.B. Welsh, L.M. Sapinoso, A.I. Su, S.G. Kern, J. Wang-Rodriguez, C.A. Moskaluk, H.F. Frierson Jr., and G.M. Hampton Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer Cancer Res 61 2001 5974 5978
44. D.K. Vanaja, J.C. Cheville, S.J. Iturria, and C.Y. Young Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression Cancer Res 63 2003 3877 3882
45. P. Liu, S. Ramachandran, M. Ali Seyed, C.D. Scharer, N. Laycock, W.B. Dalton, H. Williams, S. Karanam, M.W. Datta, D.L. Jaye, and C.S. Moreno Sex-determining region Y box 4 is a transforming oncogene in human prostate cancer cells Cancer Res 66 2006 4011 4019
46. M.S. Arredouani, B. Lu, M. Bhasin, M. Eljanne, W. Yue, J.M. Mosquera, G.J. Bubley, V. Li, M.A. Rubin, T.A. Libermann, and M.G. Sanda Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer Clin Cancer Res 15 2009 5794 5802
47. D.R. Rhodes, J. Yu, K. Shanker, N. Deshpande, R. Varambally, D. Ghosh, T. Barrette, A. Pandey, and A.M. Chinnaiyan ONCOMINE: a cancer microarray database and integrated data-mining platform Neoplasia 6 2004 1 6
48. C.J. Creighton, A.M. Hilger, S. Murthy, J.M. Rae, A.M. Chinnaiyan, and D. El-Ashry Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors Cancer Res 66 2006 3903 3911
49. S. Chrissobolis, Z. Zhang, D.A. Kinzenbaw, C.M. Lynch, A.F. Russo, and F.M. Faraci Receptor activity-modifying protein-1 augments cerebrovascular responses to calcitonin gene-related peptide and inhibits angiotensin II-induced vascular dysfunction Stroke 41 2010 2329 2334
50. R. Sabharwal, Z. Zhang, Y. Lu, F.M. Abboud, A.F. Russo, and M.W. Chapleau Receptor activity-modifying protein 1 increases baroreflex sensitivity and attenuates angiotensin-induced hypertension Hypertension 55 2010 627 635
51. O. Nagakawa, M. Ogasawara, H. Fujii, K. Murakami, J. Murata, H. Fuse, and I. Saiki Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate cancer cells Cancer Lett 133 1998 27 33
52. O. Nagakawa, M. Ogasawara, J. Murata, H. Fuse, and I. Saiki Effect of prostatic neuropeptides on migration of prostate cancer cell lines Int J Urol 8 2001 65 70
53. M. Toda, T. Suzuki, K. Hosono, I. Hayashi, S. Hashiba, Y. Onuma, H. Amano, Y. Kurihara, H. Kurihara, H. Okamoto, S. Hoka, and M. Majima Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide Proc Natl Acad Sci U S A 105 2008 13550 13555
54. K. Suzuki, Y. Kobayashi, and T. Morita Serum calcitonin gene-related peptide levels in untreated prostate cancer patients Int J Urol 13 2006 781 784
55. X.J. Yu, C.Y. Li, K.Y. Wang, and H.Y. Dai Calcitonin gene-related peptide regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes by activation of ERK1/2 MAPK Regul Pept 137 2006 134 139
56. T.T. Tomic, H. Gustavsson, W. Wang, K. Jennbacken, K. Welen, and J.E. Damber Castration resistant prostate cancer is associated with increased blood vessel stabilization and elevated levels of VEGF and Ang-2 Prostate 72 2012 705 712
57. P. Zhang, W. Liu, J. Zhang, H. Guan, W. Chen, X. Cui, Q. Liu, and A. Jiang Gene expression profiles in the PC-3 human prostate cancer cells induced by NKX3.1 Mol Biol Rep 37 2010 1505 1512
58. H. Zhang, M.H. Muders, J. Li, F. Rinaldo, D.J. Tindall, and K. Datta Loss of NKX3.1 favors vascular endothelial growth factor-C expression in prostate cancer Cancer Res 68 2008 8770 8778
59. C. Korherr, H. Gille, R. Schafer, K. Koenig-Hoffmann, J. Dixelius, K.A. Egland, I. Pastan, and U. Brinkmann Identification of proangiogenic genes and pathways by high-throughput functional genomics: TBK1 and the IRF3 pathway Proc Natl Acad Sci U S A 103 2006 4240 4245
60. E. Helgason, Q.T. Phung, and E.C. Dueber Recent insights into the complexity of Tank-binding kinase 1 signaling networks: the emerging role of cellular localization in the activation and substrate specificity of TBK1 FEBS Lett 587 2013 1230 1237
61. A.B. Fernandez-Martinez, A.M. Bajo, M. Isabel Arenas, M. Sanchez-Chapado, J.C. Prieto, and M.J. Carmena Vasoactive intestinal peptide (VIP) induces malignant transformation of the human prostate epithelial cell line RWPE-1 Cancer Lett 299 2010 11 21
62. A.B. Fernandez-Martinez, A.M. Bajo, A. Valdehita, M. Isabel Arenas, M. Sanchez-Chapado, M.J. Carmena, and J.C. Prieto Multifunctional role of VIP in prostate cancer progression in a xenograft model: suppression by curcumin and COX-2 inhibitor NS-398 Peptides 30 2009 2357 2364
63. B. Collado, M.J. Carmena, C. Clemente, J.C. Prieto, and A.M. Bajo Vasoactive intestinal peptide enhances growth and angiogenesis of human experimental prostate cancer in a xenograft model Peptides 28 2007 1896 1901
64. H. Bonkhoff, N. Wernert, G. Dhom, and K. Remberger Relation of endocrine-paracrine cells to cell proliferation in normal, hyperplastic, and neoplastic human prostate Prostate 19 1991 91 98
65. Y. Xie, D.W. Wolff, M.F. Lin, and Y. Tu Vasoactive intestinal peptide transactivates the androgen receptor through a protein kinase A-dependent extracellular signal-regulated kinase pathway in prostate cancer LNCaP cells Mol Pharmacol 72 2007 73 85
66. E. Hernes, S.D. Fossa, A. Berner, B. Otnes, and J.M. Nesland Expression of the epidermal growth factor receptor family in prostate carcinoma before and during androgen-independence Br J Cancer 90 2004 449 454
67. T. Zellweger, C. Ninck, M. Bloch, M. Mirlacher, P.A. Koivisto, H.J. Helin, M.J. Mihatsch, T.C. Gasser, and L. Bubendorf Expression patterns of potential therapeutic targets in prostate cancer Int J Cancer 113 2005 619 628
68. A. Wells EGF receptor Int J Biochem Cell Biol 31 1999 637 643
69. Z. Culig, G. Bartsch, and A. Hobisch Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth Mol Cell Endocrinol 197 2002 231 238
70. P.C. Smith, A. Hobisch, D.L. Lin, Z. Culig, and E.T. Keller Interleukin-6 and prostate cancer progression Cytokine Growth Factor Rev 12 2001 33 40
71. T.D. Chung, J.J. Yu, T.A. Kong, M.T. Spiotto, and J.M. Lin Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines Prostate 42 2000 1 7
72. B. Wegiel, A. Bjartell, Z. Culig, and J.T. Persson Interleukin-6 activates PI3K/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival Int J Cancer 122 2007 1521 1529
73. H.L. Adler, M.A. McCurdy, M.W. Kattan, T.L. Timme, P.T. Scardino, and T.C. Thompson Elevated levels of circulating interleukin-6 and transforming growth factor-beta1 in patients with metastatic prostatic carcinoma J Urol 161 1999 182 187
74. N. Hoosein, M. Abdul, R. McCabe, E. Gero, L. Deftos, M. Banks, S. Hodges, L. Finn, and C. Logothetis Clinical significance of elevation in neuroendocrine factors and interleukin-6 in metastatic prostate cancer Urol Oncol 1 1995 246 251
75. D.A. Twillie, M.A. Eisenberger, M.A. Carducci, W.S. Hseih, W.Y. Kim, and J.W. Simons Interleukin-6: a candidate mediator of human prostate cancer morbidity Urology 45 1995 542 549
76. D.E. Drachenberg, A.A. Elgamal, R. Rowbotham, M. Peterson, and G.P. Murphy Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer Prostate 41 1999 127 133
77. A. Hobisch, R. Ramoner, D. Fuchs, S. Godoy-Tundidor, G. Bartsch, H. Klocker, and Z. Culig Prostate cancer cells (LNCaP) generated after long-term interleukin 6 (IL-6) treatment express IL-6 and acquire an IL-6 partially resistant phenotype Clin Cancer Res 7 2001 2941 2948