Human Immunodeficiency Virus Type 1-Like DNA Sequences and Immunoreactive Viral Particles with Unique Association with Breast Cancer

Abstract

RAK antigens p120, p42, and p25 exhibit molecular and immunological similarity to the proteins encoded by human immunodeficiency virus type 1 (HIV-1) and are expressed by 95% of breast and gynecological cancer cases in women and prostate cancer cases in men. The binding of an epitope-specific anti-HIV-1 gp120 monoclonal antibody (MAb) (amino acids 308 to 322) to cancer RAK antigens has been found to be inhibited by a peptide derived from variable loop V3 of HIV-1. Breast cancer DNAs of 40 patients were PCR amplified with HIV-1 gp41-derived primers, and all of the samples were found to be positive. The DNA fragments amplified in seven blindly selected breast cancer samples were sequenced. The breast cancer DNA sequences showed at least 90% homology to the HIV-1 gene for gp41. Antisense oligonucleotides complementary to the HIV-1-like sequences inhibited reverse transcriptase activity and inhibited the growth of breast cancer cells in vitro. Viral particles detected in breast cancer cell lines were strongly immunogold labeled with the anti-HIV-1 gp120 MAb. The results obtained strongly suggest that the long-postulated breast cancer virus may, in fact, be related to HIV-1.

Pathology of the Breast Associated With HIV/AIDS

“…The ovine maedi‐visna virus (MVV), a lentivirus of the Retroviridae family similar to HIV (78), also targets mammary glands causing mastitis and gynecomastia (79). Novel RAK antigens (p120, p42, and p25), which are expressed in 95–100% of studied breast cancer cases, have been shown to exhibit molecular, immunologic, and genetic similarities to the proteins encoded by HIV‐1 (80–82). Normal breast tissue does not appear to express these unique RAK cancer markers.…”

Giant Syncytia and Virus-Like Particles in Ovarian Carcinoma Cells Isolated from Ascites Fluid

“…Although RAK antigens exhibit homology to HIV-1 antigens, these cancer markers can be easily distinguished from HIV-1 infection by using any antibody directed against the glycosylated form of HIV-1 gp120 or MAb 5025 (19) or any other anti-HIV-1 MAb which does not cross-react with cancer antigens. Moreover, MAb RAK-BrI binds to RAK p120, p42, and p25 in cancer cells, but only to gp160 or gp120 of HIV-1 (18), which automatically eliminates a possibility of infection. In the current studies, HIV-like antigens were detected in all ASC syncytia.…”

“…The viral origin of markers RAK was recently confirmed by finding breast cancer and cervical cancer-associated viral particles, immunoreactive with a monoclonal antibody (MAb) specific for HIV-1 gp120 (MAb 5023) (18). Moreover, antisense oligonucleotides complementary to the HIV-1-like sequences inhibited reverse transcriptase activity in breast and cervical cancer cells and inhibited proliferation of these cells (18). Over 90% of ovarian cancer patients also express antigen RAK in the blood and antigens p120, p45, and p24 in the malignant tissue (20,25).…”

“…It is noteworthy that HIV-1-related DNA sequences are absent in normal tissues of cancer patients, which suggests an exogenous (viral) origin. The viral origin of markers RAK was recently confirmed by finding breast cancer and cervical cancer-associated viral particles, immunoreactive with a monoclonal antibody (MAb) specific for HIV-1 gp120 (MAb 5023) (18). Moreover, antisense oligonucleotides complementary to the HIV-1-like sequences inhibited reverse transcriptase activity in breast and cervical cancer cells and inhibited proliferation of these cells (18).…”

“…PCR with HIV-1 gp41-derived primers revealed breast and prostate cancer-associated DNA sequences with over 90% homology to HIV-1 genomes (17,18,24). These novel DNA sequences have been deposited in the GenBank as cancerassociated gene RAK alpha.…”