No abstract

No abstract

No abstract

Spontaneously immortalized human mammary epithelial cells MCF-10A were transfected with an activated c-Ha-ras oncogene. Transfected cells (MCF-10T) acquire a malignant phenotype, as already reported. Studies of 125I-2'-deoxyuridine incorporation in cultures given graded doses of hydrocortisone (HC), cholera toxin (CT), epidermal growth factor (EGF), and transforming growth factor alpha (TGF-alpha) showed that though MCF-10T had become almost independent on exogenous EGF and TGF-alpha, they continued to respond to the synergistic effect of HC and CT plus EGF. Both lines were phenotypically characterized with an immunoradiometric assay in live cells. Expression of MHC class-I molecules, human milk-fat-globule-I antigen, and EGF receptor was reduced in ras-transfected cells, although other differentiation markers were unchanged. Exogenous EGF down-regulated the expression of functional EGF-R, selectively in transformed cells. TGF-alpha failed to modulate EGF-R. In contrast, HC strongly stimulated the expression of EGF-R while depressing MHC class-I molecules. Thus, it appears that in vivo HC may co-operate with TGF-alpha and EGF in promoting the growth of transformed mammary cells. This hormone might also favor the escape from immune surveillance by reducing the expression of surface differentiation markers.

The frequency with which int-I and int-2 are rearranged in mouse mammary tumors by mouse mammary tumor virus (MMTV)-induced insertional mutagenesis is a consequence of the host genetic background. In 75 % of C3H mammary tumors, int-i is rearranged by MMTV insertion, whereas only 30% of BALB/cfC3H tumors contain a virus-induced rearrangement of int-1. This difference is significant (P < 0.005) and could not be accounted for by the potentially additive effect of the genetically transmitted Mtv-1-encoded virus in C3H mice. Similarly, MMTV-induced rearrangement of the int-2 gene in mammary tumors of the Rlll mouse strain (59%) occurred at a significantly (P < 0.025) higher frequency than in BALB/cfRlll (25%) mammary tumors. Moreover, in BALB/cfRlll mammary tumors, there is evidence that rearrangement of int-i and int-2 does not occur independently (P < 0.025). These results suggest that the long history of inbreeding for high tumor incidence of C3H and Rlll mouse strains has selected for the fixation of host mutations which either complement the action of the particular int gene or affect the sensitivity of specific subpopulations of mammary epithelium to infection by particular strains of MMTV.

The C3H and RIII mammary tumor viruses (MTV) carried by BALB/cfC3H and BALB/cfRIII breeding females have been quantified and compared in milk samples, after partial purification with a sucrose density gradient. The samples were collected at identical times during the first 3 lactation periods from individual mice (6 per strain), standardized for age at delivery and size of litter. Milk samples from 6 MTV negative BALB/c controls have also been analyzed. Data for comparison are expressed in optical density units (ODU) and refer to the protein content of the whole milk using MTV-negative Balb/c milk as blank. The results have shown 1) an increase of MTV released through milk in each MTV-carrying female from the first (average ODU, 0.542) to the second (1,351) and third (2.105) lactation, 2) individual variations, and 3) a significant difference in release between C3H and RIII MTV, the latter being more than double (average ODU, 1.801) in respect to the former (0.847). The apparent discrepancy between these results and the bioactivity in BALB/c mice of C3H and RIII MTV, significantly lower for the latter, is discussed.

No abstract

The correlation of the most important prognostic indicators was evaluated in 75 breast cancer cases. Estrogen-progesterone receptors and proliferating activity were analyzed by immunocytochemical methods (ER-ICA, PR-ICA, Ki-67). Both steroid receptors were inversely correlated with the proliferating activity (ER-ICA vs Ki-67, p less than 0.003; PR-ICA vs. Ki-67, p less than 0.0001). No correlation was found between steroid receptors or cell kinetics and tumor size or lymph node status. These findings confirm the relevance of biochemical and kinetic parameters as independent markers in breast cancer and suggest a routine use of the simple immunocytochemical methods in assessing the biological behavior of tumors.