Expression profiling of the cellular processes in uterine leiomyomas: omic approaches and IGF-2 association with leiomyosarcomas.
OBJECTIVE
This study utilized both cDNA microarray and 2D protein gel electrophoresis technology to investigate the multiple interactions of the genes and proteins involved in the pathophysiology of uterine leiomyomas. Also, Gene Ontology (GO) analysis was used to systematically characterize the global expression profiles, which were found to correlate with the leiomyosarcomas.


METHODS
The uterine leiomyoma biopsies were obtained from patients in the Department of Obstetrics and Gynecology, The Catholic University of Korea. Differentially expressed transcriptome and proteome, in 6 paired leiomyoma and normal myometrium, were profiled. The total RNAs from the leiomyoma and normal myometrium were labeled with Cy5 and Cy3. All specimens were punch-biopsy-obtained, and frozen in liquid nitrogen.


RESULTS
Screening of up to 17,000 genes identified 71 that were either up-regulated or down-regulated (21 and 50, respectively). The gene expression profiles were classified into 420 mutually dependent functional sets, resulting in 611 cellular processes, according to the gene ontology. Also, the protein analysis, using 2D gel electrophoresis, identified 33 proteins (17 up-regulated and 16 down-regulated) with more than 500 total spots, which were classified into 302 cellular processes. O f these functional profilings, transcriptomes and proteoms down-regulations were shown in the cell adhesion, cell motility, organogenesis, enzyme regulator, structural molecule activity and responses to external stimulus functional activities, which are supposed to play important roles in the pathophysiology. In contrast, up-regulation was only shown in the nucleic acid binding activity. The CDKN2A, ADH1A, DCX, IGF2, CRABP2 and KIF5C were found to increase the reliability of this study, and correlate with the leiomyosarcomas.


CONCLUSIONS
Potentially significant pathogenetic cellular processes showed that down-regulated functional profiling has an important impact on the discovery of the pathogenic pathways in leiomyomas and leiomyosarcomas. GO analysis can also overcome the complexity of the expression profiles of cDNA microarrays and 2D protein analyses, via a cellular process level approach. Thereby, a valuable prognostic candidate gene, with real relevance to disease-specific pathogenesis, can be found at cellular process levels.
Bae
Su Mi
SM
Catholic Research Institutes of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Kim
Yong-Wan
YW
Lee
Joon Mo
JM
Namkoong
Sung Eun
SE
Kim
Chong Kook
CK
Ahn
Woong Shick
WS
Mol Cell. 2000 May;5(5):831-40
10882119
Genome Biol. 2003;4(1):R7
12540299
Nature. 1995 Jun 8;375(6531):503-6
7777060
Fertil Steril. 1981 Oct;36(4):433-45
7026295
Epidemiol Infect. 1994 Oct;113(2):275-81
7523157
Fertil Steril. 2002 Jul;78(1):114-21
12095500
Hum Reprod Update. 2001 Jan-Feb;7(1):8-14
11212080
Blood. 2001 Apr 1;97(7):1920-4
11264152
Hum Pathol. 1998 Apr;29(4):359-63
9563785
J Soc Gynecol Investig. 2003 Apr;10(3):161-71
12699880
N Engl J Med. 1988 Dec 1;319(22):1434-40
3185662
Science. 1997 Oct 24;278(5338):680-6
9381177
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11679-83
7972123
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10757-62
9724777
Electrophoresis. 2002 Aug;23(15):2490-504
12210208
Cancer Res Treat. 2003 Aug;35(4):304-13
26680952
Nat Med. 2002 May;8(5):518-21
11984598
Am J Pathol. 2001 Sep;159(3):1121-7
11549605
J Lab Clin Med. 2003 May;141(5):297-308
12761473
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
9843981
J Cell Biol. 1999 Feb 22;144(4):789-801
10037799
Curr Biol. 2002 Apr 30;12(9):712-23
12007414
Cancer. 2003 Sep 1;98(5):1029-38
12942572
Gynecol Oncol. 2002 Jun;85(3):507-10
12051882
Methods Enzymol. 1999;303:179-205
10349646