Rabbit Anti-Human OLFM1 (a.a. 153-420) Polyclonal antibody

Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (>= 4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.

PURPOSE. Olfactomedin 2 (OLFM2) belongs to the family of olfactomedin domain-containing proteins. Genetic data suggest its association with glaucoma in Japanese patients. However, its functions are still elusive. In this study, the properties of mammalian OLFM2 were investigated. METHODS. Expression of the rat and mouse Olfm2 gene was studied by using real-time PCR and in situ hybridization. Substitutions were introduced into OLFM2 by mutagenesis in vitro. Intracellular localization of OLFM2 was studied by confocal microscopy after transient transfection in HEK293 cells. Interaction of OLFM2 with olfactomedin 1 (Olfm1), olfactomedin 3 (Olfm3), myocilin, and gliomedin was studied by using co-immunoprecipitation. RESULTS. Two major human OLFM2 mRNAs encode secreted proteins with a length of 454 and 478 amino acids. OLFM2 is more closely related to OLFM1 and -3 than to any other family members. Olfm2 showed the most dynamic expression pattern compared with Olfm1 and -3 during mouse eye development and was expressed preferentially in the developing retinal ganglion cell layer. Among three OLFM2 substitutions tested (T86M, R144Q, and L420S), only L420S completely blocked secretion of the protein. OLFM2 interacted with Olfm1 and -3, but not with myocilin and gliomedin. Co-transfection of the L420S mutant with wild-type Olfm1 and -3 significantly inhibited secretion of Olfm1 and -3. CONCLUSIONS. Highly conserved OLFM2 protein may play an important role in the course of retinal and eye development. Severe mutations in one of the closely related olfactomedin domain-containing proteins (Olfm1-3) may block the secretion and probably the activity of all three family members, leading to more pronounced diseases of the retina than the knockout of individual genes. (Invest Ophthalmol Vis Sci. 2011;52:2584-2592) DOI:10.1167/iovs.10-6356