Functional characterization of the progestagen‐associated endometrial protein gene in human melanoma

Abstract

Utilizing gene microarray profiling of melanoma samples, we have recently identified a novel gene overexpressed in both thick primary and metastatic melanomas. This gene, progestagen-associated endometrial protein (PAEP), has never before been implicated in the oncogenic processes of melanoma, with its true function in oncogenesis and tumour progression relatively unknown. Overexpression of the PAEP gene in freshly procured thick primary and metastatic melanoma samples (58%) and daughter cell lines (77%) is confirmed by quantitative RT-PCR, immunohistochemistry, Western blotting and mass spectrometric analysis. We suggest that PAEP gene overexpression is involved with melanoma tumour progression as well as an aggressive phenotype. Transfection of melanoma cells with PAEP small interfering RNA (siRNA) reveals a significant decrease in soft agar colony formation and a marked inhibition of both cell migration and cell invasion. Furthermore, we establish stable melanoma transfectants via PAEP lentiviral small hairpin RNA (shRNA), examine their growth characteristics in a murine xenograft model and reveal that tumour growth is significantly inhibited in two separate melanoma cell lines. Our data strongly implicate the PAEP gene as a tumour growth promoter with oncogenic properties and a potential therapeutic target for patients with advanced melanoma.

Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

“…Increasing glycodelin concentrations have been linked to deregulated PLAU and MMP9 activity and inhibition of trophoblast invasiveness (11). This finding is supported by observations in melanoma cells, where cell migration and invasion were strongly inhibited after glycodelin silencing (16). In our study, we observed the expression of glycodelin in metastatic lymph nodes and distant metastases.…”

“…Atypical glycodelin expression is observed in hormone-related breast cancer, endometrial cancer, and ovarian cancer (15). Recent studies have demonstrated glycodelin expression in melanoma cells and lung cancer (16,17). Geneexpression data from our group revealed that PAEP is expressed in a lung cancer cell line as well (18).…”

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

“…Song et al (9) demonstrated that PAEP is also involved in neovascularization during tumor growth (9). However, our previous study presumed that PAEP is a tumor promoter in melanoma (10), suggesting contradictory results as compared to other studies.…”

“…The gene has also been demonstrated to be differentially involved in certain tumor (18,19). Several studies have suggested that PAEP inhibits tumor cell growth and promotes cell differentiation as a tumor suppressive factor; however, other authors have demonstrated that PAEP increases the invasion of endometrial adenocarcinoma cells (20) and melanoma (10). Therefore, the function of PAEP gene expression in tumorigenesis and tumor progression remains unclear.…”

“…Thus, secretion of SPP-1 is directly related to the presence of PAEP. Our previous study demonstrated that silencing the PAEP gene expression decreased the migration and invasion of melanoma cells and inhibited tumor growth in a human xenograft model (10). These results suggested that PAEP may act as a tumor-promoting factor influencing the biological behavior of melonom and knockdown of PAEP gene was essential for this observation.…”