Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata.
Human uterine leiomyomata are the most common tumors in women of reproductive age. The pathogenesis of leiomyomata remains unknown. An animal model of Eker rats with deleted tuberous sclerosis complex gene 2 (tuberin) shows increased incidence of leiomyomata. The role of tuberin in human leiomyomata is unknown. In this study, we designed a tissue microarray with tissue cores of leiomyomata and the matched myometrium from 60 hysterectomy specimens. We examined the expression of tuberin and tuberous sclerosis complex gene 1 product hamartin, proteins of the insulin-signaling pathway, steroid receptors and some of their cofactors, and human mobility group gene A2 by immunohistochemistry. We found that nearly half of the cases displayed either reduction or loss of tuberin in leiomyomata compared with matched normal myometrium. No change of hamartin was noted. Furthermore, a significant reduction of glucocorticoid receptor was found in leiomyomata with reduced tuberin. The proteins insulin like growth factor 1, insulin-like growth factor receptor beta, AKT kinase, and phosphatidylinositol 3-kinase were upregulated. Nearly half of leiomyomata show upregulation of human mobility group gene A2, along with the steroid receptor cofactors. Our findings suggest that there are two broad groups of uterine leiomyomata. One group is associated with an alteration of tuberin and glucocorticoid receptor. The other group is associated with upregulation of human mobility group gene A2 and steroid receptor cofactors.
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Jianjun
J
Wei
Luis
L
Chiriboga
Masashi
M
Mizuguchi
Herman
H
Yee
Khush
K
Mittal
D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D016000:Cluster Analysis; D005260:Female; D024243:HMGB1 Protein / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D007889:Leiomyoma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D011987:Receptors, Steroid / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; D011987:Receptors, Steroid; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D007334:Insulin-Like Growth Factor I