Over-Expression of Ly6/Plaur Domain Containing 6b (Lypd6b) in Ovarian Cancer

Abstract

Advanced stage serous ovarian cancer is metastatic disease with poor prognosis requiring the identification of new therapeutic and prognostic targets. We examined the gene expression of 20 advanced stage serous ovarian cancers compared to eight cases of normal ovarian surface epithelium using Affymetrix human genome U133 Plus2.0 GeneChip ® array and identified the over-expression of LY6/PLAUR domain containing 6B (LYPD6B) in cancers. The function of LYPD6B is unknown, however, the LYPD6B sequence encodes an amino acid region of high similarity to snake venom toxins and the PLAUR domain, a domain present in genes involved in regulating invasion and metastasis. We identified three LYPD6B mRNA variants and termed them as LYPD6B_a, LYPD6B_b and LYPD6B_c. We found that the variant LYPD6B_a is predominantly expressed in late stage serous ovarian cancers by quantitative real time PCR. All three variants of the recombinant V5-tag LYPD6B proteins are expressed on the cell membrane of OVCAR3 ovarian cancer cells. Four different shRNAs were used in knockdown of mRNA and protein of LYPD6B in OVCAR3 cells. However, these LYPD6B knockdown cells did not show any change of cell morphology, cell proliferation and cell migration. We noted a dramatic over-expression of several other LY6/PLAUR domain containing transcripts in ovarian cancer. Of these, LYPD1 expression is higher than that of LYPD6B. In summary we identified the high expression of LYPD6B and LYPD1 in ovarian cancers and that these may encode proteins useful in diagnostic or prognostic purposes or for the evaluation of recurrence in ovarian cancer.