Abstract
The association of human breast cancer with sequences similar to the mouse mammary tumor virus (MMTV) has been shown, but convincing evidence for the presence of viral particles in breast tumors has been lacking. We have described the complete proviral structure of a retrovirus in human breast cancer. This provirus, designated as human mammary tumor virus (HMTV), was 95% homologous to MMTV and revealed features of a replication-competent virus. We have therefore investigated the production of viral particles in primary cultures of human breast cancer (MSSM). Cells isolated from ascites or pleural effusions of patients with metastatic breast cancer contained viral sequences in their DNA, expressed Env protein, and showed retroviral particles by electron microscopy. Viral particles from culture media exhibited morphologic features of beta-retroviruses sedimenting at buoyant densities of 1.12 to 1.18 g/mL in sucrose gradients and showed reverse transcriptase activity. cDNA sequences from virion RNA were synthesized, amplified, and sequenced and all the virion genes were detected and 70% of the virion RNA was sequenced. The sequence homologies were, respectively, 85% to 95% compared with the MMTV and HMTV proviruses we have previously described. These results clearly show that breast cancer cells in primary cultures produced HMTV viral particles that are similar to the mouse virus and which may play a role in human breast cancer pathogenesis.
Highlights
The association of a virus similar to mouse mammary tumor virus (MMTV) with human breast cancer has been shown by us and others [1,2,3,4,5,6,7,8]
The primary cultures of human breast cancer cells used in these experiments were obtained from discarded ascitic fluids or discarded pleural effusions from 10 patients with human mammary tumor virus (HMTV) envpositive breast cancer
The results reported here clearly show for the first time that primary cultures of human breast cancer cells produce viral www.aacrjournals.org particles with morphologic and molecular characteristics of a h-retrovirus similar to MMTV
Summary
The association of a virus similar to mouse mammary tumor virus (MMTV) with human breast cancer has been shown by us and others [1,2,3,4,5,6,7,8]. We reported that a 660-bp sequence of the MMTV env gene is present in 38% of American women’s breast cancers [1] and is expressed in most of the env-positive tumors [2]. Subsequent amplification experiments showed other gene segments homologous to their MMTV counterparts, but not to any of the human endogenous retroviruses including K-10 (HERV-K10), Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/). Nepomnaschy: ILEX, CONICET, National Academy of Medicine, Buenos Aires, Argentina
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