Search

Murine mammary tumors induced by the Murine Mammary Tumor Virus (MMTV) were chosen to study the expression of the NM23 gene during the metastatic process because of their viral etiology, different from that of the previously reported experimental tumor systems. NM23 mRNA levels are higher in non metastatic tumors than in metastatic ones. Moreover, the NM23 expression is higher in tumors induced by the C3H variant of the MMTV than in tumors induced by the RIII variant. These data are a further support to the hypothesis of a basic role of the NM23 gene in the down-regulation of tumor progression.

We have previously shown that mice simultaneously infected with the murine mammary tumor virus (MuMTV) and with certain slow murine leukemia viruses (MLV) have an increased resistance to the pathological effects of both agents. Here we report that milk-transmitted MuMTV also delays the development of the acute erythroleukemia induced by Friend leukemia virus (FLV), and retards, or prevents in some cases, the development of long-term lymphomas caused by its helper component. This is confirmed by the observation that the average life span of MuMTV-carrying mice infected with FLV or its helper component is prolonged by over 30% as compared to that of MuMTV-free animals infected with the same agents and by the finding that the replication of Friend viruses is reduced in mice neonatally exposed to MuMTV. Since the antibody responses of mice to MuMTV and to FLV were not cross-reactive, we searched for antiviral activity in the tissues of mice exposed to MuMTV, FLV, or the helper component of FLV. Low levels of interferon-alpha/beta were consistently detected in spleen extracts from mice infected with all these agents but could not be demonstrated in the spleens of uninfected BALB/c mice; thus, the chronic production of endogenous interferon is likely to play a major role in the reciprocal interference in vivo between retroviruses belonging to different genera.

The ability to metastasize via the bloodstream of mammary tumors occurring in Balb/cfC3H and Balb/cfRIII mice (two substrains of identical Balb/c genotype carrying milk-transmitted C3H or RIII murine mammary tumor virus (MuMTV) infection, respectively) has been compared in MuMTV-free Balb/c virgin female recipients given intravenous tumor cell suspensions or subcutaneous solid tumor transplants from mammary tumor-bearing Balb/cfC3H and Balb/cfRIII breeding female donors. Tumor cell suspensions different for MuMTV inducing variant, growth rate, tumor size, and clinical duration, injected intravenously to Balb/c virgin female recipients, have been compared with respect to the foci of lung colonization induced in recipient hosts. The results obtained indicate that MuMTV variant, growth rate and clinical duration of the primary mammary tumor, but not the size of the primary tumor, significantly influence the lung colonization. Similar results were obtained with solid subcutaneous transplants of the same mammary tumors. The significance of these results for the understanding of the general mechanisms of tumor metastases is discussed.

The morphological growth of the mammary glandular tree from 3 to 18 months of age has been quantified in three groups of genetically identical virgin female mice: BALB/c mice free of milk-transmitted mouse mammary tumor virus (MMTV) infection and BALB/cfC3H and BALB/cfRIII mice carrying milk-transmitted MMTV infection of C3H or RIII origin, respectively. Mice were killed at 3-month intervals, and their mammary glands were prepared for stereoscopic examination as whole mounts. Any cluster of alveoli from 0.1 mm in diameter was counted and measured at 0.1-mm intervals. The small clusters of alveoli (less than or equal to 0.3 mm) were used to measure the amount of lobuloalveolar differentiation. The larger clusters of alveoli, the hyperplastic alveolar nodules, and the mammary tumors were used to measure the frequency of tumor cell transformations. Lobuloalveolar differentiation in BALB/c mice was increased significantly by both C3H (p less than 0.001) and RIII (p less than 0.001) MMTV infections. RIII MMTV induced a significantly higher lobuloalveolar differentiation as compared to that induced by C3H MMTV (p less than 0.001). C3H MMTV showed a significantly higher capability in inducing hyperplastic alveolar nodules and mammary tumors as compared to that of RIII MMTV (p less than 0.001). The conclusions were that two different activities are carried out by MMTV, namely, lobuloalveolar differentiation and noduligenesis, and that these two MMTV activities are distinct from each other.