Trophinin is a potent prognostic marker of ovarian cancer involved in platinum sensitivity

Abstract

Ovarian cancer is the leading cause of death in women with gynecological malignancies, with prognosis of advanced stage tumors determined by chemotherapeutic response and the success of tumor resection. Since aberrant RAS pathway activation is frequent in ovarian cancer, study of in vitro RAS-induced transformation and accompanying genomic expression changes in ovarian surface epithelial cells is imperative for development of new therapeutic modalities and for understanding tumorigenesis. cDNA microarray analysis revealed TROPHONIN (TRO), a homophilic adhesion molecule involved in blastocyst implantation, was among the genes most downregulated by RAS induction. TRO expression is higher in cisplatin-sensitive cancer cell lines and positively correlates with prognoses in ovarian cancers. TRO knockdown by RNA interference conferred cisplatin resistance and led to increased invasiveness of cultured ovarian cancer cells. These findings underscore the importance of TRO in tumorigenesis, and suggest that TRO may be a useful biomarker for cisplatin sensitivity and invasive potential.

Trophinin: What embryo implantation teaches us about human cancer.

“…TRO-positive ovarian cancer cell lines are highly sensitive to cisplatin treatment compared to trophinin-negative lines. 47 This finding is supported by analysis of a chemosensitivity profile database: cisplatin-sensitive lines expressed higher levels of TRO than did resistant cells. As de-regulation of RAS pathways confers cisplatin resistance in ovarian cancers, these observations suggest that trophinin modulates platinum sensitivity through a pro-apoptotic mechanism and via an effect on RAS signaling in ovarian cancer.…”

“…43,44 In this review, any type of epithelial cancers in men and women producing hCG are considered trophoblastic cancer and discussed below for their relation to embryo implantation, as hCG and trophinin are closely linked in human cancers. [45][46][47] Many human endometrial adenocarcinoma lines are available, 48 whereas no mouse endometrial adenocarcinoma line has been established. This evidence may be related to the fact that no endometrial adenocarcinoma occurs in the mouse.…”

“…45,46,56 However, in ovarian cancer trophinin expression signals a better prognosis than trophinin-negative tumors. 47 Ovarian cancer and breast cancer may share cancer modulatory mechanisms, as hCG suppresses breast cancer growth. 51,59 Further study of human embryo implantation should help us understand these contrasting activities.…”

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma

“…However, the treatment can still be viewed largely as a 'shot in the dark' and the tools available to help predict who will respond optimally to which treatment are still relatively crude. Some molecules, such as BRCA1 (Quinn et al, 2007), soluble Fas levels (Chaudhry et al, 2008), Death Receptor 4 and TNF receptor 2 (TNFR2) (Dong et al, 2008), EF24 (Selvendiran et al, 2007), and trophinin (Baba et al, 2007), have been shown to correlate with cisplatin resistance in human ovarian cancer. The molecular markers involved in the activity of chemotherapeutic agents can shed light on the successes and failures of treatment in ovarian cancer patients and can also provide a basis for individualised therapy.…”

TP53 Status is Associated with Thrombospondin1 Expression In vitro

“…For cDNA synthesis, 1 μg of total RNA was incubated for 60 min at 42°C with oligo (dT) primers and 20 units of AMV reverse transcriptase in 1× reverse transcriptase buffer supplemented with 5 mM of MgCl 2 , 1 mM of each dNTP, and 25 units of RNase inhibitor in a final volume of 20 μl (Roche Diagnostics Cooperation, Indianapolis, IN, USA). Methodologies for determining TP53 mutation status and immunohistochemical protein expression, population doubling time of the cells, invasive capacity, and chemotherapy-induced growth inhibition have been previously described (15–18). Western blot analysis of TP53 protein was also performed before and after exposure to radiation and hypoxia.…”