Decreased Expression of Retinol-Binding Proteins is Associated with Malignant Transformation of the Ovarian Surface Epithelium

Roberts, David; Williams, Stephen J.; Cvetkovic, Dusica; Weinstein, Jillian K.; Godwin, Andrew K.; Johnson, Steven W.; Hamilton, Thomas C.
January 2002
DNA & Cell Biology;Jan2002, Vol. 21 Issue 1, p11
Academic Journal
We have developed a modified form of suppression subtractive hybridization (SSH) that allows multiple specimens of distinct phenotypic groups to be compared for consistent differences in gene expression. We applied this system to identify genes that were expressed in normal rat ovarian surface epithelial (ROSE) cells but whose expression was lost/downregulated in four independently transformed rat ovarian cancer cell lines. Northern blot analysis using 14 of 28 nonredundant cDNA fragments from this difference library showed that the mRNA transcripts were present in normal ROSE cells but lost or markedly downregulated in four related transformed cell lines. Of particular interest, cellular retinol-binding protein 1 (CRBP1) and retinol-binding protein (RBP), two genes whose products are involved in retinol transport and metabolism, were found to be downregulated in this ovarian cancer model system. To determine if this change had relevance to human ovarian cancer, we evaluated a series of human ovarian cancer cell lines and a limited number of frozen human ovarian tumors and found lost or decreased expression of CRBP1 and RBP relative to expression in human ovarian surface epithelial (HOSE) cells. We hypothesize that the loss of CRBP1 and RBP expression disrupts retinol metabolism and retinoic acid production, which may facilitate the occurrence of genetic damage leading to the malignant transformation of the ovarian surface epithelium, the cells from which ovarian cancer arises.


Related Articles

  • Errata: A structural basis for the unique binding features of the human vitamin D-binding protein. Verboven, Christel; Rabijns, Anja; De Maeyer, Marc; Van Baelen, Hugo; Bouillon, Roger; De Ranter, Camiel // Nature Structural Biology;Apr2002, Vol. 9 Issue 4, p316 

    Presents the correction for an article published in the 2002 issue of the journal 'Nature Structural Biology,' which focuses on the structural basis for the unique binding features of the human vitamin D-binding protein.

  • Diagnostic value of urinary retinol-binding protein in childhood nephrotic syndrome. Dillon, Susannah C.; Taylor, G. Michael; Shah, Vanita // Pediatric Nephrology;1998, Vol. 12 Issue 8, p643 

    Urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and retinol-binding protein (RBP), sensitive markers of renal tubular damage and dysfunction respectively, were evaluated in paired remission and relapse urine samples from 16 patients (median age 12 years), with minimal change nephrotic...

  • Vitamin D Binding Protein-Macrophage Activating Factor (DBP-maf) Inhibits Angiogenesis and Tumor Growth in Mice. Kisker, Oliver; Onizuka, Shinya; Becker, Christian M.; Fannon, Michael; Flynn, Evelyn; D'Amato, Robert; Zetter, Bruce; Folkman, Judah; Ray, Rahul; Swamy, Narasimha; Pirie-Shepherd, Steven // Neoplasia;Jan/Feb2003, Vol. 5 Issue 1, p32 

    Presents a study that investigated a selectively deglycosylated form of vitamin D binding protein (DBP-maf) generated from systematically available DBP by a human pancreatic cancer cell line. Analysis of the characteristics of DBP-maf; Findings of a histological examination of DBP-maf treated...

  • Cellular Retinol-Binding Protein Expression and Breast Cancer. Kuppumbatti, Yuvarani S.; Bleiweiss, Ira J. // JNCI: Journal of the National Cancer Institute;03/15/2000, Vol. 92 Issue 6, p475 

    Provides information on a study that analyzed the expression of cellular retinol-binding protein in normal and malignant breast cancer tissues. Function of retinoic acid receptor and retinoid X receptor nuclear receptor families; Methodology; Results and discussion.

  • Two vitamin D3-dependent calcium binding proteins increase calcium reabsorption by different mechanisms I. Effect of CaBP 28K. Bouthtiauy, Ihssane; Lajeunesse, Daniel; Christakos, Sylvia; Brunette, Michèle G. // Kidney International;Feb1994, Vol. 45 Issue 2, p461 

    Several clearance and micropuncture studies suggest that vitamin D deficiency decreases calcium (Ca2+) reabsorption by the nephron. In confirmation of these observations, we reported recently that in vitamin D depleted rabbits. Ca2+ transport by both the luminal and the basolateral membranes of...

  • Transthyretin: a review from a structural perspective. Hamilton, J. A.; Benson, M. D. // Cellular & Molecular Life Sciences;Sep2001, Vol. 58 Issue 10, p1491 

    Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding of both ligands. Transthyretin is also...

  • Serum Retinol Binding Protein (RBP4) Levels Predict Intraabdominal Fat Mass. Graham, Timothy E.; Kloting, Nora; Berndt, Janin; Kralisch, Susan; Kovacs, Peter; Wason, Christopher J.; Fasshauer, Mathias; Schon, Michael R.; Stumvoll, Michael; Bluher, Matthias; Kahn, Barbara B. // Diabetes;Jun2007 Supplement 1, Vol. 56, pA365 

    Increased intraabdominal fat is associated with insulin resistance and increased cardiovascular risk. Adipose tissue secretes proteins (adipokines) that regulate systemic insulin action. Adipokine production varies among fat depots. The adipokine, RBP4, is increased in obesity, impaired glucose...

  • Biochemical characterization of recombinant chicken riboflavin carrier protein. Madhavi Bangaru; Anjali Karande // Molecular & Cellular Biochemistry;Jan2008, Vol. 308 Issue 1/2, p1 

    Abstract  Chicken Riboflavin Carrier Protein (cRCP) transports riboflavin from the maternal circulation to the egg yolk for fetal development. The cRCP is a globular protein and structurally very stable due to the presence of nine intra-molecular disulphide bonds. The cRCP...

  • Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein. Quadro, Loredana; Blaner, William S.; Salchow, Daniel J.; Vogel, Silke; Piantedosi, Roseann; Gouras, Peter; Freeman, Sarah; Cosma, Maria P.; Colantuoni, Vittorio; Gottesman, Max E. // EMBO Journal;9/1/99, Vol. 18 Issue 17, p4633 

    Retinol-binding protein (RBP) is the sole specific transport protein for retinol (vitamin A) in the circulation, and its single known function is to deliver retinol to tissues. Within tissues, retinol is activated to retinoic acid, which binds to nuclear receptors to regulate transcription of...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics