Abstract
The protooncogene c-myc is a major factor in tumourigenesis. Whereas c-myc overexpression
is considered to be a general feature of many tumours, we have recently demonstrated
c-myc underexpression in adrenocortical cancer by a meta-analysis. We hypothesise
that c-myc underexpression might be a central event in adrenortical tumourigenesis
based on network topology modelling and previous experimental observations. In this
brief hypothesis, we present our arguments and their possible relevance.
Key words
adrenal - tumour - meta-analysis - network
References
- 1
Soucek L, Evan GI.
The ups and downs of Myc biology.
Curr Opin Genetics Dev.
2010;
20
91-95
- 2
Nesbit CE, Tersak JM, Prochownik EV.
MYC oncogenes and human neoplastic disease.
Oncogene.
1999;
18
3004-3016
- 3
Szabó PM, Tamási V, Molnár V, Andrásfalvy M, Tömböl Z, Farkas R, Kövesdi K, Patócs A,
Tóth M, Szalai C, Falus A, Rácz K, Igaz P.
Meta-analysis of adrenocortical tumor genomics data: novel pathogenic pathways revealed.
Oncogene.
2010;
29
3163-3172
- 4
Giordano TJ, Kuick R, Else T, Gauger PG, Vinco M, Bauersfeld J, Sanders D, Thomas DG,
Doherty G, Hammer G.
Molecular classification and prognostication of adrenocortical tumors by transcriptome
profiling.
Clin Cancer Res.
2009;
15
668-676
- 5
de Reyniès A, Assié G, Rickman DS, Tissier F, Groussin L, René-Corail F, Dousset B,
Bertagna X, Clauser E, Bertherat J.
Gene expression profiling reveals a new classification of adrenocortical tumors and
identifies molecular predictors of malignancy and survival.
J Clin Oncol.
2009;
27
1108-1115
- 6
Tömböl Z, Szabó PM, Molnár V, Wiener Z, Tölgyesi G, Horányi J, Riesz P, Reismann P,
Patócs A, Likó I, Gaillard RC, Falus A, Rácz K, Igaz P.
Integrative molecular bioinformatics study of human adrenocortical tumors: microRNA,
tissue-specific target prediction, and pathway analysis.
Endocr Relat Cancer..
2009;
16
895-906
- 7
Barabasi AL, Albert R.
Emergence of scaling in random networks.
Science.
1999;
286
509-512
- 8
Crucitti, Latora V, Marchiori M.
Model for cascading failures in complex networks.
Phys Rev.
2004;
E 69
045104-1–045104-4
- 9
Liu J, Voutilainen R, Kahri AI, Heikkilä P.
Expression patterns of the c-myc gene in adrenocortical tumors and pheochromocytomas.
J Endocrinol.
1997;
152
175-181
- 10
Heikkilä P, Arola J, Salmi A, Kahri AI.
ACTH-induced c-myc proton-oncogene expression precedes antimitogenic effect during
differentiation of fetal rat adrenocortical cells.
J Endocrinol.
1995;
145
379-385
- 11
Liu J, Voutilainen R, Kahri AI, Heikkilä P.
Expression of the c-myc gene in human adrenals: regulation by adrenocorticotropin
in primary cultures.
J Endocrinol.
1996;
148
523-529
- 12
Coulter CL.
Fetal adrenal development: insight gained from adrenal tumors.
Trends Endocrinol Metab.
2005;
16
235-242
- 13
Larsson LS, Henriksson MA.
The Yin and Yang functions of the Myc oncoprotein in cancer development and as targets
for therapy.
Exp Cell Res.
2010;
316
1429-1437
- 14
Gandarillas A, Watt FM.
c-Myc promotes differentiation of human epidermal stem cells.
Genes Dev.
1997;
11
2869-2882
- 15
Bettess MD, Dubois N, Murphy MJ, Dubey C, Roger C, Robine S, Trumpp A.
c-Myc is required for the formation of intestinal crypts but dispensable for homeostasis
of the adult intestinal epithelium.
Mol Cell Biol.
2005;
25
7868-7878
- 16
Toftgard R, Roop DR, Yuspa SH.
Proto-oncogene expression during two-stage carcinogenesis in mouse skin.
Carcinogenesis.
1985;
6
655-657
- 17
Watson JV, Stewart J, Evan GI, Ritson A, Sikora K.
The clinical significance of flow cytometric c-myc oncoprotein quantitation in testicular
cancer.
Br J Cancer.
1986;
53
331-337
- 18
Fassnacht M, Allolio B.
Clinical management of adrenocortical carcinoma.
Best Pract Res Clin Endocrinol Metab.
2009;
23
273-289
- 19
Lepique AP, Moraes Ms, Rocha KM, Eichler CB, Hajj GNM, Schwindt TT, Armelin HA.
c-Myc protein is stabilized by fibroblast growth factor 2 and destabilized by ACTH
to control cell cycle in mouse Y1 adrenocortical cells.
J Mol Endocrinol.
2004;
33
623-638
- 20
Baudino TA, McKay C, Pendeville-Samain H, Nilsson JA, Maclean KH, White EL, Davis AC,
Ihle JN, Cleveland JL.
c-Myc is essential for vasculogenesis and angiogenesis during development and tumor
progression.
Genes Dev.
2002;
16
2530-2543
- 21
Bernini GP, Moretti A, Bonadio AG, Menicagli M, Viacava P, Naccarato AG, Iacconi P,
Miccoli P, Salvetti A.
Angiogenesis in human normal and pathologic adrenal cortex.
J Clin Endocrinol Metab.
2002;
87
4961-4965
Correspondence
Dr. P. IgazMD, MSc, PhD
2nd Department of Medicine
Faculty of Medicine
Semmelweis University
Szentkiralyi street 46
1088 Budapest
Hungary
Telefon: +36/1/4591 500
Fax: +36/1/2660 816
eMail: igapet@bel2.sote.hu