title: Motility-related actinin alpha-4 is associated with advanced and metastatic ovarian carcinoma.
abstract: Advanced and metastatic ovarian cancer is a leading cause of death from gynecologic malignancies. A more detailed understanding of the factors controlling invasion and metastasis may lead to novel anti-metastatic therapies. To model cellular interactions that occur during intraperitoneal metastasis, comparative cDNA microarray analysis and confirmatory real-time reverse transcription PCR (RT-PCR) were employed to uncover changes in gene expression that may occur in late stage ovarian cancer in response to microenvironmental cues, particularly native three-dimensional collagen I. Gene expression in human ovarian carcinoma tissues was evaluated on the RNA and protein level using real-time RT-PCR and immunohistochemistry. Cell invasion and migration were evaluated in a collagen invasion assay and a scratch wound assay. Three-dimensional collagen I culture led to differential expression of several genes. The role of actinin alpha-4 (ACTN4), a cytoskeleton-associated protein implicated in the regulation of cell motility, was examined in detail. ACTN4 RNA and protein expression were associated with advanced and metastatic human ovarian carcinoma. This report demonstrates that a cytoskeletal-associated protein ACTN4 is upregulated by three-dimensional collagen culture conditions, leading to increased invasion and motility of ovarian cancer cells. Expression of ACTN4 in human ovarian tumors was found to be associated with advanced-stage disease and peritoneal metastases.
authors: Department of Chemical and Biochemical Engineering, Northwestern University, Chicago, IL, USA.
authors: Maria V
authors: MV
authors: Barbolina
authors: Brian P
authors: BP
authors: Adley
authors: David L
authors: DL
authors: Kelly
authors: Angela J
authors: AJ
authors: Fought
authors: Denise M
authors: DM
authors: Scholtens
authors: Lonnie D
authors: LD
authors: Shea
authors: M Sharon
authors: MS
authors: Stack
mesh_terms: D000185:Actinin / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D014162:Transfection; D014945:Wound Healing
chemical_list: C111453:ACTN4 protein, human; D024042:Collagen Type I; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000185:Actinin