Overexpression of integrin-β1 in leiomyoma promotes cell spreading and proliferation.

Context: Uterine leiomyoma, the most common tumors found in the women of the reproductive age, may cause abnormal uterine bleeding and be life threatening. Compared with myometrium, leiomyoma contains excessive extracellular matrix (ECM). However, the pathological roles of ECM in the development of leiomyoma remain largely unknown.

The role of human papillomavirus type 16 E6/E7 oncoproteins in cervical epithelial-mesenchymal transition and carcinogenesis.

Cervical cancer is the most common malignancy in females worldwide. This study investigated the prevalence of the E6/E7 oncoproteins of human papillomavirus (HPV) type 16, which are important in fibroblast growth factor (FGF) 2- and 4-induced epithelial-mesenchymal transition (EMT) and cervical tumorigenesis. We investigated the functional interaction between HPV16 E6/E7-transfected Cx cells (CxWJ cells) and treatment with FGF2 and 4, according to the expression of α-smooth muscle actin (α-SMA), vimentin and E-cadherin protein as well as cell growth and invasive ability.

Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the development of endometriosis.

Dysfunction in macrophage-mediated phagocytosis of aberrant cells that undergo retrograde transport to the peritoneal cavity is considered an important factor in the development of endometriosis. However, the mechanisms responsible for the loss of function of macrophages remain largely unknown. Herein, we report that prostaglandin (PG) E(2), via the EP2 receptor-dependent signaling pathway, inhibits the expression of CD36 in peritoneal macrophages, resulting in reduced phagocytic ability.

Neutrophils and macrophages promote angiogenesis in the early stage of endometriosis in a mouse model.

Substantial evidence suggests that inflammatory cytokines, immune cells, and angiogenesis are important for endometriosis. In this study, we investigated the role of the sequential events in the development of endometriosis in a mouse model. Uterine tissue was transplanted into the peritoneum of ovariectomized mice and then supplemented with estrogen or vehicle.

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 mammalian target of rapamycin-p70 ribosomal S6 kinase but not phosphatidylinositol 3-kinase-Akt signaling is responsible for fibroblast growth factor-9-induced cell proliferation.

Fibroblast growth factor-9 (FGF9) is a potent mitogen that stimulates normal and cancer cell proliferation though the signaling mechanism is not fully understood. In this study, we aimed to unravel the signaling cascades mediate FGF9 actions in human uterine endometrial stromal cell. Our results demonstrate that the mitogenic effect of FGF9 is transduced via two parallel but additive signaling pathways involving mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase.

Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen.

Fibroblast growth factor-9 (FGF-9) is a steroid-regulated mitogen and survival factor for nerve and mesenchymal cells. In the current study, we determined the expression pattern and functional roles of FGF-9 in the ectopic endometriotic lesions. We found that FGF-9 and its receptors were effectively expressed by ectopic endometriotic tissues.

Pathogenetic roles of angiogenic factors in pyogenic granulomas in pregnancy are modulated by female sex hormones.

Background: An abundance of microvessels is the major phenotype of pyogenic granuloma, which has been considered a hormone-related lesion based on clinical observations. Although angiogenic factors and inflammatory cytokines have been implied to play roles in the pathogenesis of pyogenic granuloma, their links to female steroid hormones still remain to be elucidated. Since apoptosis is important in limiting inflammation, we also investigated whether steroid hormones could protect granuloma cells from apoptosis and, therefore, lead to overreactive inflammatory response.

Estrogen stimulates expression of p21Waf1/Cip1 in mouse uterine luminal epithelium.

p21Waf1/Cip1 was originally identified as an inhibitor of the cell cycle. Recent evidence suggests that it can act as a positive regulator of the cell cycle under the influence of some growth stimulators. We investigated the effects of ovarian steroids on the expression of p21, DNA synthesis, and mitosis in the uterus.

Pathogenetic Roles of Angiogenic Factors in Pyogenic Granulornas in Pregnancy Are Modulated by Female Sex Hormones.

Background: An abundance of microvessels is the major phenotype of pyogenic granuloma, which has been considered a hormone-related lesion based on clinical observations. Although angiogenic factors and inflammatory cytokines have been implied to play roles in the pathogenesis of pyogenic granuloma, their links to female steroid hormones still remain to be elucidated. Since apoptosis is important in limiting inflammation, we also investigated whether steroid hormones could protect granuloma cells from apoptosis and, therefore, lead to over-reactive inflammatory response.

Fibroblast growth factor-9 is an endometrial stromal growth factor.

Fibroblast growth factor-9 (FGF-9) is an autocrine/paracrine growth factor considered to be important for the growth and survival of motorneurons and prostate. In this study, we found that FGF-9 was expressed at high levels in normal uterine endometrium, especially during the late proliferative phase, which is coincident with the rise of estradiol and the time of uterine endometrial proliferation. Using quantitative RT-PCR analysis, we found that FGF-9 mRNA was expressed primarily by endometrial stromal cells.