ABSTRACT
Mouse mammary tumor virus (MMTV) is a hormonally regulated, oncogenic virus of mice. MMTV-like virus DNA has previously been detected in human breast cancers, liver disease, and liver cancers. It is hypothesized that local hormonal effects might be of primary importance in determining MMTV-like virus detection in human tumors. MMTV-like virus envelope (env) DNA was determined using nested PCR in 89 ovarian, 147 prostate, 50 endometrial, 141 skin, and 51 lung cancers. Viral-positive sequences were compared with published MMTV-like viral sequences from human breast cancer, liver cancer and MMTV. Immunohistochemistry for estrogen receptor (ER-alpha) and progesterone receptor (PgR) was performed on a subset of tumors. MMTV-like virus env DNA was detected in ovarian cancers (14/89; 16%), prostate cancers (53/147; 36%), endometrial cancers (5/50; 10%), skin cancers (13/141; 9%) but not in lung cancers (0/51). Phylogenetic analysis of the viral-positive sequences showed no clustering of the isolates according to tissue type. A significant association was observed between the presence of hormone receptors and detection of MMTV-like virus in the human cancers screened (P = 0.01). A significant association between MMTV-like virus and PgR was noted in skin cancers (P = 0.003). Therefore, unlike the mouse model, the detection of MMTV-like env sequences in human cancers in addition to breast indicates that MMTV-like viral expression is not breast cancer-specific and may relate to hormone-dependent viral expression.
Subject(s)
Hormones/pharmacology , Neoplasms/virology , Retroviridae/isolation & purification , DNA, Viral/chemistry , DNA, Viral/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/virology , Estrogen Receptor alpha/analysis , Female , Humans , Immunohistochemistry , Lung Neoplasms/pathology , Lung Neoplasms/virology , Male , Mammary Tumor Virus, Mouse/genetics , Molecular Sequence Data , Ovarian Neoplasms/pathology , Ovarian Neoplasms/virology , Polymerase Chain Reaction , Prostatic Neoplasms/pathology , Prostatic Neoplasms/virology , Receptors, Progesterone/analysis , Retroviridae/genetics , Skin Neoplasms/pathology , Skin Neoplasms/virology , Viral Envelope Proteins/geneticsABSTRACT
CONTEXT: GH abuse is a significant problem in many sports, and there is currently no robust test that allows detection of doping beyond a short window after administration. OBJECTIVE: Our objective was to evaluate gene expression profiling in peripheral blood leukocytes in-vivo as a test for GH doping in humans. DESIGN: Seven men and thirteen women were administered GH, 2 mg/d sc for 8 wk. Blood was collected at baseline and at 8 wk. RNA was extracted from the white cell fraction. Microarray analysis was undertaken using Agilent 44K G4112F arrays using a two-color design. Quantitative RT-PCR using TaqMan gene expression assays was performed for validation of selected differentially expressed genes. RESULTS: GH induced an approximately 2-fold increase in circulating IGF-I that was maintained throughout the 8 wk of the study. GH induced significant changes in gene expression with 353 in women and 41 in men detected with a false discovery rate of less than 5%. None of the differentially expressed genes were common between men and women. The maximal changes were a doubling for up-regulated or halving for down-regulated genes, similar in magnitude to the variation between individuals. Quantitative RT-PCR for seven target genes showed good concordance between microarray and quantitative PCR data in women but not in men. CONCLUSION: Gene expression analysis of peripheral blood leukocytes is unlikely to be a viable approach for the detection of GH doping.
