Evaluation of the mTOR pathway in ocular (uvea and conjunctiva) melanoma

Melanoma Research

Volumn 20, Issue 2, 2010, Pages 107-117

  Pópulo, Helena ^a,b   Soares, Paula ^a,b   Rocha, Ana Sofia ^a   Silva, Paula ^a   Lopes, José Manuel ^a,b,c  

^a UNIVERSITY OF PORTO   (Portugal)

^b University of Porto   (Portugal)

^c HOSPITAL DE SÃO JOÃO   (Portugal)

Author keywords

BRAF; Conjunctiva melanoma; Mammalian target of rapamycin (mTOR) pathway; NRAS; Ocular melanoma; Uvea melanoma

Indexed keywords

B RAF KINASE; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; SERINE; THREONINE;

ADULT; AGED; ARTICLE; CARCINOGENESIS; CLINICAL ARTICLE; CLINICAL FEATURE; CONJUNCTIVA MELANOMA; CONJUNCTIVA TUMOR; CONTROLLED STUDY; DOWN REGULATION; GENE EXPRESSION; GENE MUTATION; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; METASTASIS; MITOSIS INDEX; ONCOGENE N RAS; PRIORITY JOURNAL; PROGNOSIS; PROTEIN PHOSPHORYLATION; TISSUE MICROARRAY; UVEA MELANOMA;

DNA MUTATIONAL ANALYSIS; EYE NEOPLASMS; GENES, RAS; HUMANS; IMMUNOHISTOCHEMISTRY; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MELANOMA; MIDDLE AGED; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS B-RAF; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; RIBOSOMAL PROTEIN S6 KINASES; SIGNAL TRANSDUCTION; TISSUE ARRAY ANALYSIS;

EID: 77949545648     PISSN: 09608931     EISSN: None     Source Type: Journal    
DOI: 10.1097/CMR.0b013e32832ccd09     Document Type: Article

References (72)

1. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84 836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998; 83:1664-1678.
2. Didolkar MS, Elias EG, Barber NA, Moore RH. Biologic behavior of ocular malignant melanoma and comparison with melanoma of the head and neck. Am J Surg 1980; 140:522-526.
3. McLean IW. The biology of haematogenous metastasis in human uveal malignant melanoma. Virchows Arch A Pathol Anat Histopathol 1993; 422:433-437.
4. McLean IW, Foster WD, Zimmerman LE, Gamel JW. Modifications of Callender's classification of uveal melanoma at the Armed Forces Institute of Pathology. Am J Ophthalmol 1983; 96:502-509.
5. Paridaens AD, Minassian DC, McCartney AC, Hungerford JL. Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases. Br J Ophthalmol 1994; 78:252-259.
6. Tuomaala S, Kivela T. Metastatic pattern and survival in disseminated conjunctival melanoma: implications for sentinel lymph node biopsy. Ophthalmology 2004; 111:816-821.
7. Anastassiou G, Heiligenhaus A, Bechrakis N, Bader E, Bornfeld N, Steuhl KP. Prognostic value of clinical and histopathological parameters in conjunctival melanomas: a retrospective study. Br J Ophthalmol 2002; 86:163-167.
8. Seregard S. Conjunctival melanoma. Surv Ophthalmol 1998; 42:321-350.
9. Gallagher RP, Lee TK. Adverse effects of ultraviolet radiation: a brief review. Prog Biophys Mol Biol 2006; 92:119-131.
10. Singh AD, Rennie IG, Seregard S, Giblin M, McKenzie J. Sunlight exposure and pathogenesis of uveal melanoma. Surv Ophthalmol 2004; 49:419-428.
11. Cruz F, Rubin BP,Wilson D, Town A, Schroeder A, Haley A, et al. Absence of BRAF and NRAS mutations in uveal melanoma. Cancer Res 2003; 63:5761-5766.
12. Gear H, Williams H, Kemp EG, Roberts F. BRAF mutations in conjunctival melanoma. Invest Ophthalmol Vis Sci 2004; 45:2484-2488.
13. Rimoldi D, Salvi S, Lienard D, Lejeune FJ, Speiser D, Zografos L, et al. Lack of BRAF mutations in uveal melanoma. Cancer Res 2003; 63:5712-5715.
14. Spendlove HE, Damato BE, Humphreys J, Barker KT, Hiscott PS, Houlston RS. BRAF mutations are detectable in conjunctival but not uveal melanomas. Melanoma Res 2004; 14:449-452.
15. Goldenberg-Cohen N, Cohen Y, Rosenbaum E, Herscovici Z, Chowers I, Weinberger D, et al. T1799A BRAF mutations in conjunctival melanocytic lesions. Invest Ophthalmol Vis Sci 2005; 46:3027-3030.
16. El-Shabrawi Y, Radner H, Muellner K, Langmann G, Hoefler G. The role of UV-radiation in the development of conjunctival malignant melanoma. Acta Ophthalmol Scand 1999; 77:31-32.
17. Damato B, Duke C, Coupland SE, Hiscott P, Smith PA, Campbell I, et al. Cytogenetics of uveal melanoma: a 7-year clinical experience. Ophthalmology 2007; 114:1925-1931.
18. Kilic E, Naus NC, van Gils W, Klaver CC, van Til ME, Verbiest MM, et al. Concurrent loss of chromosome arm 1p and chromosome 3 predicts a decreased disease-free survival in uveal melanoma patients. Invest Ophthalmol Vis Sci 2005; 46:2253-2257.
19. Parrella P, Sidransky D, Merbs SL. Allelotype of posterior uveal melanoma: implications for a bifurcated tumor progression pathway. Cancer Res 1999; 59:3032-3037.
20. Damato B. Developments in the management of uveal melanoma. Clin Exp Ophthalmol 2004; 32:639-647.
21. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007; 12:9-22.
22. Huang S, Houghton PJ. Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol 2003; 3:371-377.
23. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006; 124:471-484.
24. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 2002; 10:457-468.
25. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, et al. Rictor, a novel binding partner of mTOR, defines a rapamycininsensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 2004; 14:1296-1302.
26. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 2002; 110:177-189.
27. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 2002; 110:163-175.
28. Oshiro N, Yoshino K, Hidayat S, Tokunaga C, Hara K, Eguchi S, et al. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells 2004; 9:359-366.
29. Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, et al. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell 2007; 25:903-915.
30. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 2004; 6:1122-1128.
31. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307:1098-1101.
32. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha. Curr Biol 1997; 7:261-269.
33. Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, et al. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 1997; 277:567-570.
34. Currie RA, Walker KS, Gray A, Deak M, Casamayor A, Downes CP, et al. Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1. Biochem J 1999; 337 (Pt 3):575-583.
35. Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998; 95:29-39.
36. Woodgett JR. Recent advances in the protein kinase B signaling pathway. Curr Opin Cell Biol 2005; 17:150-157.
37. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, et al. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 1996; 15:6541-6551.
38. Inoki K, Li Y, Zhu T,Wu J, Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002; 4:648-657.
39. Inoki K, Li Y, Xu T, Guan KL. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 2003; 17:1829-1834.
40. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 2003; 13:1259-1268.
41. Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J. Rheb binds and regulates the mTOR kinase. Curr Biol 2005; 15:702-713.
42. Kovacina KS, Park GY, Bae SS, Guzzetta AW, Schaefer E, Birnbaum MJ, et al. Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. J Biol Chem 2003; 278:10189-10194.
43. Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H, et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 2004; 166:213-223.
44. Shah OJ, Hunter T. Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Mol Cell Biol 2006; 26:6425-6434.
45. Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest 2008; 118:3065-3074.
46. Huang J, Dibble CC, Matsuzaki M, Manning BD. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol 2008; 28:4104-4115.
47. Tee AR, Blenis J. mTOR, translational control and human disease. Semin Cell Dev Biol 2005; 16:29-37.
48. Dancey JE. Therapeutic targets: MTOR and related pathways. Cancer Biol Ther 2006; 5:1065-1073.
49. Fecher LA, Cummings SD, Keefe MJ, Alani RM. Toward a molecular classification of melanoma. J Clin Oncol 2007; 25:1606-1620.
50. Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R, et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci U S A 2001; 98:10314-10319.
51. Sawyers CL. The cancer biomarker problem. Nature 2008; 452:548-552.
52. Yu K, Toral-Barza L, Discafani C, Zhang WG, Skotnicki J, Frost P, et al. mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer 2001; 8:249-258.
53. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417:949-954.
54. Demunter A, Ahmadian MR, Libbrecht L, Stas M, Baens M, Scheffzek K, et al. A novel N-ras mutation in malignant melanoma is associated with excellent prognosis. Cancer Res 2001; 61:4916-4922.
55. Stahl JM, Cheung M, Sharma A, Trivedi NR, Shanmugam S, Robertson GP. Loss of PTEN promotes tumor development in malignant melanoma. Cancer Res 2003; 63:2881-2890.
56. Davies MA, Stemke-Hale K, Tellez C, Calderone TL, Deng W, Prieto VG, et al. A novel AKT3 mutation in melanoma tumours and cell lines. Br J Cancer 2008; 99:1265-1268.
57. Robertson GP. Functional and therapeutic significance of Akt deregulation in malignant melanoma. Cancer Metastasis Rev 2005; 24:273-285.
58. Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, Bosenberg MW, et al. Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res 2004; 64:7002-7010.
59. Karbowniczek M, Spittle CS, Morrison T, Wu H, Henske EP. mTOR is activated in the majority of malignant melanomas. J Invest Dermatol 2008; 128:980-987.
60. Bundscherer A, Hafner C, Maisch T, Becker B, Landthaler M, Vogt T. Antiproliferative and proapoptotic effects of rapamycin and celecoxib in malignant melanoma cell lines. Oncol Rep 2008; 19:547-553.
61. Molhoek KR, Brautigan DL, Slingluff CL Jr. Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor Rapamycin. J Transl Med 2005; 3:39.
62. Abdel-Rahman MH, Yang Y, Zhou XP, Craig EL, Davidorf FH, Eng C. High frequency of submicroscopic hemizygous deletion is a major mechanism of loss of expression of PTEN in uveal melanoma. J Clin Oncol 2006; 24:288-295.
63. Saraiva VS, Caissie AL, Segal L, Edelstein C, Burnier MN Jr. Immunohistochemical expression of phospho-Akt in uveal melanoma. Melanoma Res 2005; 15:245-250.
64. Greene F, Page D, Fleming I, Fritz A, Balch C, Haller D, et al. AJCC cancer staging manual. 6th ed. New York: Springer; 2002.
65. Cruz J, Reis-Filho JS, Silva P, Lopes JM. Expression of c-met tyrosine kinase receptor is biologically and prognostically relevant for primary cutaneous malignant melanomas. Oncology 2003; 65:72-82.
66. Soares P, Fonseca E, Wynford-Thomas D, Sobrinho-Simoes M. Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms? J Pathol 1998; 185:71-78.
67. Castro P, Rebocho AP, Soares RJ, Magalhaes J, Roque L, Trovisco V, et al. PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. J Clin Endocrinol Metab 2006; 91:213-220.
68. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006; 441:424-430.
69. Slipicevic A, Holm R, Nguyen MT, Bohler PJ, Davidson B, Florenes VA. Expression of activated Akt and PTEN in malignant melanomas: relationship with clinical outcome. Am J Clin Pathol 2005; 124:528-536.
70. Farber M, Schutzer P, Mihm MC Jr. Pigmented lesions of the conjunctiva. J Am Acad Dermatol 1998; 38 (6 Pt 1):971-978.
71. Weber A, Hengge UR, Urbanik D, Markwart A, Mirmohammadsaegh A, Reichel MB, et al. Absence of mutations of the BRAF gene and constitutive activation of extracellular-regulated kinase in malignant melanomas of the uvea. Lab Invest 2003; 83:1771-1776.
72. ZuidervaartW, van Nieuwpoort F, Stark M, Dijkman R, Packer L, Borgstein AM, et al. Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS. Br J Cancer 2005; 92:2032-2038.