Entry Name Melanoma - Rattus norvegicus (rat)
Description Melanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes. The only known environmental risk factor is exposure to ultraviolet (UV) light and in people with fair skin the risk is greatly increased. Melanoma pathogenesis is also driven by genetic factors. Oncogenic NRAS mutations activate both effector pathways Raf-MEK-ERK and PI3K-Akt. The Raf-MEK-ERK pathway may also be activated via mutations in the BRAF gene. The PI3K-Akt pathway may be activated through loss or mutation of the inhibitory tumor suppressor gene PTEN. These mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Melanoma development has been shown to be strongly associated with inactivation of the p16INK4a/cyclin dependent kinases 4 and 6/retinoblastoma protein (p16INK4a/CDK4,6/pRb) and p14ARF/human double minute 2/p53 (p14ARF/HMD2/p53) tumor suppressor pathways. MITF and TP53 are implicated in further melanoma progression.
Class Human Diseases; Cancer: specific typesBRITE hierarchy
Pathway map Ortholog table Organism Rattus norvegicus (rat) [GN:
rno ]
Gene 170633 Fgf3; fibroblast growth factor 3 precursor [KO:K04358 ]
116499 Fgf4; fibroblast growth factor 4 precursor [KO:K04358 ]
60662 Fgf5; fibroblast growth factor 5 isoform 1 precursor [KO:K04358 ]
29348 Fgf7; fibroblast growth factor 7 precursor [KO:K04358 ]
25443 Fgf10; fibroblast growth factor 10 precursor [KO:K04358 ]
29368 Fgf17; fibroblast growth factor 17 isoform 1 precursor [KO:K04358 ]
29369 Fgf18; fibroblast growth factor 18 precursor [KO:K04358 ]
170579 Fgf22; fibroblast growth factor 22 precursor [KO:K04358 ]
170582 Fgf19; fibroblast growth factor 19 precursor [KO:K22603 ]
170580 Fgf21; fibroblast growth factor 21 precursor [KO:K22429 ]
170583 Fgf23; fibroblast growth factor 23 precursor [KO:K22428 ]
24446 Hgf; hepatocyte growth factor preproprotein [KO:K05460 ]
24482 Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459 ]
25266 Pdgfa; platelet-derived growth factor subunit A precursor [KO:K04359 ]
24628 Pdgfb; platelet-derived growth factor subunit B precursor [KO:K17386 ]
79429 Pdgfc; platelet-derived growth factor C precursor [KO:K05450 ]
66018 Pdgfd; platelet-derived growth factor D precursor [KO:K05450 ]
25313 Egf; pro-epidermal growth factor precursor [KO:K04357 ]
25718 Igf1r; insulin-like growth factor 1 receptor isoform 2 precursor [KO:K05087 ] [EC:2.7.10.1 ]
25267 Pdgfra; platelet-derived growth factor receptor alpha precursor [KO:K04363 ] [EC:2.7.10.1 ]
367858 Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833 ]
58960 Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369 ] [EC:2.7.12.2 ]
85243 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
170911 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
366508 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
134484121 LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922 ] [EC:2.7.1.153 ]
25513 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
60664 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
29741 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
64639 Bad; bcl2-associated agonist of cell death [KO:K02158 ]
25163 Cdkn2a; cyclin-dependent kinase inhibitor 2A [KO:K06621 ]
114851 Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
24708 Rb1; retinoblastoma-associated protein [KO:K06618 ]
684111 E2f2; transcription factor E2F2 isoform X2 [KO:K09389 ]
25112 Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
291005 Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
299626 Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
25094 Mitf; microphthalmia-associated transcription factor isoform 1 [KO:K09455 ]
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Miller AJ, Mihm MC Jr.
Title Melanoma.
Journal Reference Authors Chin L.
Title The genetics of malignant melanoma: lessons from mouse and man.
Journal Reference Authors Takata M, Saida T.
Title Genetic alterations in melanocytic tumors.
Journal Reference Authors Chudnovsky Y, Khavari PA, Adams AE.
Title Melanoma genetics and the development of rational therapeutics.
Journal Reference Authors Merlino G.
Title Cancer biology: the weakest link?
Journal Reference Authors Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR.
Title Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.
Journal Reference Authors Levy C, Khaled M, Fisher DE.
Title MITF: master regulator of melanocyte development and melanoma oncogene.
Journal Reference Authors Tsao H, Goel V, Wu H, Yang G, Haluska FG.
Title Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma.
Journal Reference Authors Gruss C, Herlyn M.
Title Role of cadherins and matrixins in melanoma.
Journal Reference Authors Thompson JF, Scolyer RA, Kefford RF.
Title Cutaneous melanoma.
Journal Reference Authors Omholt K, Platz A, Kanter L, Ringborg U, Hansson J.
Title NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression.
Journal Clin Cancer Res 9:6483-8 (2003)
Reference Authors Hussein MR.
Title The TP53 tumor suppressor gene and melanoma tumorigenesis: is there a relationship?
Journal Reference Authors Lazar-Molnar E, Hegyesi H, Toth S, Falus A.
Title Autocrine and paracrine regulation by cytokines and growth factors in melanoma.
Journal Related KO pathway LinkDB All DBs
