transforming-growth-factor-beta and Cystadenocarcinoma--Papillary

Ovarian epithelial tumor (OET) is a silent disease of late diagnosis and poor prognosis. Currently treatment options are limited and patient response to treatment is difficult to predict so there is a serious need to delineate the real pathogenesis to predict tumour prognosis. Prohibitin (PHB) is an evolutionarily protein that regulates the cell cycle. TGF-β has been shown to be a positive and negative regulator of cellular proliferation and differentiation. The present study provides an overview on the role played by PHB1, TGF-β and LH in ovarian cancer.. The study was conducted on 60 patients with ovarian tumors (benign, borderline and malignant) and 20 healthy volunteers. LH and TGF-β serum levels were measured by ELISA. Expression of prohibitin and LHR-mRNA were assessed by IHC and TaqMan® real time gene expression assay, respectively.. Serum levels of LH and TGF-β were significantly decreased among borderline and malignant groups. There was significant over-expression of LHRmRNA in malignant group. Prohibitin expression was significantly increased in malignant ovarian tissue. Strong negative correlations were found between LHR mRNA expression and serum LH levels, and between IHC score of prohibitin and serum levels of LH among patients with borderline ovarian tumors.. Steady decline of LH and TGF-B serum levels, from benign cystadenoma to borderline tumor to carcinoma, suggests their inhibitory role against OET cell growth. Increased PHB1 expression in OET suggests its proliferative activity that can be regulated by luteinisation and/or TGF-β. Furthermore increased LHR mRNA tissue expression can provide hope for using LH in treatment of some types of ovarian cancers.

Topics: Adult; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Cystadenoma, Mucinous; Cystadenoma, Papillary; Female; Gene Expression Regulation, Neoplastic; Humans; Luteinization; Luteinizing Hormone; Middle Aged; Neoplasm Proteins; Ovarian Neoplasms; Ovary; Prohibitins; Receptors, LH; Repressor Proteins; RNA, Messenger; RNA, Neoplasm; Transforming Growth Factor beta

Resistance to the potent growth inhibitory effects of transforming growth factor-beta (TGF-beta) is a characteristic of many malignancies. TGF-beta insensitivity has been attributed to alterations in the number and function of the TGF-beta receptors as well as disturbances of downstream signal transduction. Paradoxically, increased levels of TGF-beta ligand have been demonstrated in several types of malignant tumors. TGF-beta also may play a role in ovarian carcinogenesis; however, the nature of this interaction has yet to be defined completely.. To explore the potential role of TGF-beta-mediated autocrine and paracrine influences in epithelial ovarian carcinoma, mRNA expression levels of the three TGF-beta ligand isoforms (TGF-beta1, TGF-beta2, and TGF-beta3) and the three TGF-beta receptors (TbetaR-I, T/betaR-II, and TbetaR-III) were examined by Northern blot analysis in both primary and recurrent ovarian carcinoma specimens. Immunohistochemical analysis was performed to localize expression of TbetaR-I and TbetaR-II, whereas the presence of genetic alterations in TbetaR-1 was examined through Southern blot analysis.. Compared with normal ovarian tissue, both primary and recurrent ovarian carcinomas demonstrated significant overexpression of the TGF-beta1 and TGF-beta3 mRNA transcripts. TGF-beta2 expression was detectable in 75% of primary and only 53% of recurrent tumor specimens. Alterations also were detected in TbetaR mRNA expression. Expression levels of TbetaR-III were significantly reduced in both primary and recurrent ovarian carcinomas. Furthermore, detectable levels of TbetaR-I and TbetaR-III mRNA transcripts were present in only 47% and 50% of recurrent ovarian tumors, respectively. Immunohistochemical staining demonstrated that TbetaR-I and TbetaR-II expression localized to tumor cells; however, receptor staining in stromal tissue also was detected. Southern blot analysis of TbetaR-I did not reveal any major genetic changes to account for the absence of TbetaR-I expression.. Alterations in expression of TGF-beta ligands and receptors consistently were greater in recurrent ovarian carcinomas compared with primary tumors, and may reflect a phenotype that promotes tumor recurrence or chemoresistance. Together, these data suggest that enhanced expression of TGF-betaI and TGF-beta3, as well as the loss of expression of TbetaR-I and TbetaR-III, contribute to ovarian carcinogenesis and/or tumor progression.

Topics: Blotting, Northern; Blotting, Southern; Cystadenocarcinoma, Papillary; Female; Humans; Ligands; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Receptors, Transforming Growth Factor beta; RNA, Messenger; Transforming Growth Factor beta

To further understand the role of growth regulation of human ovarian cancer cells by transforming growth factor (TGF) beta 1.. The cell proliferation, cAMP synthesis, gene expression, and induction of programmed cell death (PCD) in human epithelial ovarian cancer cell line HO-8910 cells exposed to TGF beta 1 in vitro were studied.. TGF beta 1 inhibited cell growth and DNA synthesis, and induced G0/G1 arrest in cell cycle. It could also trigger PCD in cells. This induction of PCD may occur within G0/G1 phase. Meanwhile, the assay also showed that TGF beta 1 could inhibit the mRNA expression of c-myc, EGFR and TGF beta 1 genes in cells.. TGF beta 1 can not only act as an autocrine to inhibit cell proliferation, but also trigger PCD in HO-8910 cells. These functions may be fulfilled through some specific signal transduction pathways.

Topics: Apoptosis; Cell Division; Cystadenocarcinoma, Papillary; Female; Humans; Ovarian Neoplasms; Transforming Growth Factor beta; Tumor Cells, Cultured

We examined the effects of transforming growth factor-beta 1 (TGF-beta 1) on intracellular parathyroid hormone-related peptide (PTHrP) production in a human ovarian cancer cell line (HOC-21).. Various concentrations of TGF-beta 1 were added to a culture medium, and the numbers of cells were counted. HOC-21 cells were cultured with or without TGF-beta 1, and intracellular PTHrP was measured by a radioimmunoassay kit that recognized the carboxy-terminal protein while counting the number of cells. Furthermore, a 125I-TGF-beta 1 binding assay was carried out. Values were analyzed statistically using an analysis of variance followed by an unpaired t-test.. Five ng/ml of TGF-beta 1 inhibited the cell growth on Day 1 after plating. The TGF-beta 1 significantly (p < 0.05) stimulated intracellular PTHrP production in a time-dependent manner, also by Day 1. A 125I-TGF-beta 1 binding study revealed that HOC-21 cells expressed a high affinity for the TGF-beta 1 receptor.. The suppression of human ovarian cancer cell proliferation by TGF-beta 1 might be involved in the production of PTHrP.

Topics: Cell Division; Culture Media; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Female; Humans; Middle Aged; Ovarian Neoplasms; Parathyroid Hormone-Related Protein; Protein Biosynthesis; Transforming Growth Factor beta; Tumor Cells, Cultured