Functional characterization of the progestagen-associated endometrial protein gene in human melanoma.
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.
Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA.
Suping
S
Ren
Suhu
S
Liu
Paul M
PM
Howell
Guangyu
G
Zhang
Lewis
L
Pannell
Rajeev
R
Samant
Lalita
L
Shevde-Samant
J Allan
JA
Tucker
Oystein
O
Fodstad
Adam I
AI
Riker
D000362:Agar; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D000071816:Glycodelin; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D014158:Transcription, Genetic; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D034741:RNA, Small Interfering; D000362:Agar