Expression and functional analysis of pituitary tumor transforming gene-1 [corrected] in uterine leiomyomas.
Pituitary tumor-transforming gene-1 (PTTG-1) is a novel protooncogene overexpressed in numerous cancer cell lines and cancers. In this study we elucidate the expression of PTTG-1 in uterine leiomyomas and its functional role in the development of this disease. By comparing 23 pairs of leiomyomas and matched pairs of myometria, we found that the expression of PTTG-1 is significantly elevated in leiomyoma. The expression of PTTG-1 is independent of the menstrual cycle and is not affected by ovarian hormones. In contrast, basic fibroblast growth factor (bFGF) time- and dose-dependently stimulates PTTG-1 expression, which results in increasing cell proliferation. Forced expression of PTTG-1 by transient transfection stimulates bFGF and VEGF expression as well as changes the expression pattern of cell cycle proteins. Western blotting analysis demonstrates that the expressions of PTTG-1, bFGF, and the cell proliferation marker, proliferating cell nuclear antigen, are positively correlated with each other, which supports the hypothesis that the positive feedback loop between PTTG-1 and bFGF increases leiomyoma cell proliferation. In summary, we have shown for the first time that PTTG-1 is up-regulated in human uterine leiomyomas and that the positive feedback loop between PTTG-1 and bFGF may be pivotal in the growth of leiomyoma cells.
Tsai
Shaw-Jenq
SJ
Department of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan.
Lin
Shu-Jeg
SJ
Cheng
Ya-Ming
YM
Chen
Hsiu-Mei
HM
Wing
Lih-Yuh C
LY
D001483:Base Sequence; D017931:DNA Primers; D005246:Feedback; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007889:Leiomyoma / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064249:Securin; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics*
D017931:DNA Primers; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D016222:Fibroblast Growth Factor 2