A placenta-specific gene ectopically activated in many human cancers is essentially involved in malignant cell processes.
The identification and functional characterization of tumor-specific genes is a prerequisite for the development of targeted cancer therapies. Using an integrated data mining and experimental validation approach for the discovery of new targets for antibody therapy of cancer, we identified PLAC1. PLAC1 is a placenta-specific gene with no detectable expression in any other normal human tissue. However, it is frequently aberrantly activated and highly expressed in a variety of tumor types, in particular breast cancer. RNAi-mediated silencing of PLAC1 in MCF-7 and BT-549 breast cancer cells profoundly impairs motility, migration, and invasion and induces a G1-S cell cycle block with nearly complete abrogation of proliferation. Knockdown of PLAC1 is associated with decreased expression of cyclin D1 and reduced phosphorylation of AKT kinase. Moreover, PLAC1 is localized on the surface of cancer cells and is accessible for antibodies which antagonize biological functions of this molecule. These features, in summary, make PLAC1 an attractive candidate for targeted immunotherapeutic approaches.
Koslowski
Michael
M
Department of Internal Medicine III, Division of Experimental and Translational Oncology, Johannes Gutenberg University, Mainz, Germany.
Sahin
Ugur
U
Mitnacht-Kraus
Rita
R
Seitz
Gerhard
G
Huber
Christoph
C
Türeci
Ozlem
O
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011257:Pregnancy Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
C415583:PLAC1 protein, human; D011257:Pregnancy Proteins; D034741:RNA, Small Interfering