Expression of selected tumor suppressor and oncogenes in endometrium of women with endometriosis.
BACKGROUND
It is becoming increasingly evident that the eutopic endometrium of women with endometriosis shows certain genetic alterations which are not found in the endometrium of disease-free women. The aim of the study was to compare the expression level of mammalian target of rapamycin (mTOR) tumor suppressor and oncogene-related genes in the endometrium of women with and without endometriosis as well as in ovarian endometriosis.


METHODS
A total of 81 regularly menstruating patients were recruited in the study. We applied the micro fluidic gene array to examine the expression of 15 human tumor suppressor and oncogenes in eutopic endometrium of 40 women with endometriosis and 41 controls without endometriosis. In 14 patients with endometriosis, gene expression was also studied in matched ovarian lesions. We studied the following genes: NF1, RHEB, mTOR, PTEN, TSC1, TSC2, KRAS, S6K1, TP53, EIF4E, LKB1, PIK3CA, BECN1, 4EBP1 and AKT1. Immunohistochemical studies were subsequently performed for selected proteins.


RESULTS
Of the 15 studied genes, we found significantly higher levels of oncogene AKT1 (P = 0.006) and tumor suppressor gene 4EBP1 (P = 0.01) mRNAs in the eutopic endometrium of women with endometriosis compared with control patients. Immunohistochemistry showed that 4EBP1 and AKT1 proteins were expressed in eutopic endometrium.


CONCLUSIONS
Our results suggest that up-regulation of AKT1 and 4EBP1 in eutopic endometrium may be associated with the pathogenesis of endometriosis, but their precise role remains to be established.
Department of Perinatology, Medical University of Bialystok, ul. Marii Sklodowskiej-Curie 24a, Bialystok, Poland. plauda@umwb.edu.pl
P
P
Laudanski
J
J
Szamatowicz
O
O
Kowalczuk
M
M
Kuźmicki
M
M
Grabowicz
L
L
Chyczewski
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000328:Adult; D018797:Cell Cycle Proteins; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D009857:Oncogenes / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis*; D011494:Protein Kinases / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D058570:TOR Serine-Threonine Kinases; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D011494:Protein Kinases; C546842:MTOR protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases