Estrogen influence on maturational pathway of murine mammary tumor virus: an immunoelectron microscopy study

Modifications induced by estrogens on hormone-independent murine mammary tumor (MMT) and its main etiological agent, the MMT virus (MMTV), are reported. High doses of estrogens released continuously from silastic capsules delay significantly the development of transplanted tumors into syngeneic hosts. Neoplastic cells present a striking cytoplasmic vacuolization and changes in the MMTV differentiation pattern. Mature virions are detected budding into cytoplasmic vacuoles instead of the extracellular space as in spontaneous and untreated transplanted tumors. This phenomenon is reversed after estrogen withdrawal at the first sign of tumor development. Application of electron microscope immunocytochemistry with colloidal gold-protein A complex and multiple monospecific antibodies reveals several interesting features. In spontaneous and untreated tumor grafts, structural viral proteins p14 and p25 appear in both intracytoplasmic capsids and mature extracellular viruses. By contrast glycoprotein gp55 labels only the envelope of mature virus. In estrogen-treated tumors this antigenic pattern is modified and the gp55 is detected in those atypical virions maturing into the intracytoplasmic vacuoles. These observations led to the conclusions that the delay in the development of hormone-independent mammary tumors caused by estrogen is due to an abnormal maturational viral process and that estrogens induce alterations of polarity in the translocation process of viral envelope glycoproteins.