Relevance of the viral RAK alpha gene in diagnosis of malignant versus nonmalignant tumors of the ovary and uterus.
Human immunodeficiency virus type 1 (HIV-1)-like antigens RAK (named after the inventor E. M. Rakowicz) p120, p42, and p25, as well as HIV-1-like segments of cancer DNA (RAK gene alpha), have been found before in breast and prostate cancers. The present study focused on determining the value of markers RAK in the diagnosis and prognosis of gynecological cancer. Expression of RAK antigens in ovarian, uterine, cervical, and vulvar cancer, in benign tumors, in tissues adjacent to cancer, and in normal tissues was tested by Western blot hybridization of the electrophoretically separated proteins with monoclonal antibody RAK BrI. The RAK alpha gene was PCR amplified with HIV-1-derived primers SK68 and SK69. RAK antigens p120, p42, and p25 were found in 95% of ovarian, uterine, and cervical cancer cases and in 75% of vulvar cancer cases. The RAK alpha gene was expressed in 100% of cancer cases, in approximately 25% of benign ovarian tumors, and in 40% of benign tumors of the uterus. DNA sequences amplified in all cancer cases exhibited more than 90% homology to HIV-1 gp41 and were encoded for the functional peptide. DNA sequences found in benign tumors contained frameshift mutations and encoded truncated or nonfunctional peptides. Such sequences have not been amplified in normal tissues. RAK antigens and the RAK alpha gene seem to belong to a lentivirus type that is highly related to HIV-1. Beyond the diagnostic value of RAK markers, future cloning of the full viral genome would lead to a better understanding of the etiology of malignant and nonmalignant tumors of reproductive organs and to the development of novel therapeutic approaches.
Rakowicz-Szulczynska
E M
EM
Department of Obstetrics and Gynecology, Laboratory of Molecular Oncology, University of Nebraska Eppley Cancer Center, and ViroTech LLC, Omaha, NE 68198-3255, USA.
D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D000090266:Chromobox Protein Homolog 5; D017931:DNA Primers; D003937:Diagnosis, Differential; D005260:Female; D016368:Frameshift Mutation; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics* / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014594:Uterine Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; C000715594:CBX5 protein, human; D017931:DNA Primers; D015488:HIV Antigens; D009363:Neoplasm Proteins; D000090266:Chromobox Protein Homolog 5; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human