Growth Of Mouse Mammary Carcinoma Research Articles

Vitamin D3 suppresses the androgen‐stimulated growth of mouse mammary carcinoma SC‐3 cells by transcriptional repression of fibroblast growth factor 8

Active metabolites of vitamin A and D are well known to act as growth inhibitors in hormone-related prostate and breast cancers. When various concentrations of 1alpha,25-dihydroxyvitamin D3 (vitamin D3), all-trans-retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) were examined, the androgen-stimulated growth of mouse mammary carcinoma SC-3 cells was inhibited by vitamin D3 alone in a dose-dependent manner. A flow cytometer analysis showed that vitamin D3 leads SC-3 cells to relative G1-growth arrest after 72 h. Characterization of vitamin D3-responsive genes using an oligonucleotide microarray demonstrated that 220 genes were upregulated at more than threefold, and 84 genes were downregulated to less than one-third, compared with the testosterone-stimulated SC-3 cells. Neither cyclin-dependent kinase inhibitors (CDKIs) nor the antiapoptotic bcl-2 gene were induced in vitamin D3-responsive genes, with the exception of a slight induction of p15(INK4B). Importantly, fgf8 was markedly repressed in response to vitamin D3. The exogenous addition of FGF8 canceled the growth suppression by vitamin D3 in SC-3 cells, suggesting that the repression of fgf8 is an indispensable step in vitamin D3-mediated growth inhibition. In reporter assays using the ARE-containing artificial construct and the natural androgen-regulated PSA promoter, co-transfection of the vitamin D receptor (VDR) and androgen receptor (AR) suppressed AR-stimulated promoter activity. In addition, vitamin D3 also suppressed androgen-stimulated promoter activity in the stably transfected SC-3 cells. Moreover, VDR repressed the core promoter activity of fgf8 in COS1 cells and in the SC-3 cells. All these findings strongly suggest that vitamin D3 serves as a negative regulator for both androgen-related and fgf8 transcriptions.

Inhibition of Growth of Mouse Mammary Carcinoma by Streptovaricin

SummaryThe growth of preexisting mammary tumors and the formation of additional tumors in MTV-positive RIII mice were significantly inhibited by streptovaricin complex. Mice bearing small tumors were given streptovaricin orally in two experiments and the rate of growth of their tumors was compared with that of matched controls. In the 1st experiment treatment was discontinued after 5 weeks while in the 2nd the animals were treated until they died. The growth rates in the two treated groups were 49% and 13% of the rates in the respective control groups. Measurements were made for 5 weeks in the 1st experiment and for 8 weeks in the second. Fewer new tumors arose in the experimental mice than in the controls. More tumors regressed in the treated mice than in the controls. Short term prophylactic treatment of MTV-negative C57BL mice with streptovaricin complex failed to protect the mice significantly from infection with MTV.

Effects of Roentgen Irradiation on the Tumor Bed: III. The Different Inhibiting Action on the Growth of Mouse Mammary Carcinoma Resulting from Pre- or Posttransplantation Irradiation

Effects of Roentgen Irradiation on the Tumor Bed: III. The Different Inhibiting Action on the Growth of Mouse Mammary Carcinoma Resulting from Pre- or Posttransplantation Irradiation

Effects of Roentgen Irradiation on the Tumor Bed: II. The Inhibiting Action of Different Dose Levels of Local Pretransplantation Roentgen Irradiation on the Growth of Mouse Mammary Carcinoma

In a previous report (1) we confirmed that local roentgen irradiation of the tumor bed inhibits the growth of transplanted mouse mammary carcinoma. These experiments illustrate the significance of the irradiated normal tissues of the host in suppressing the growth of the tumor, because the tumor cells inoculated into the irradiated bed had received no irradiation. In the previous experiments emphasis was placed on the comparison between the growth of the tumor transplants in irradiated and shielded sites within the same animals. A single dose of 1500 r/air was given to one leg of young ZBC mice, and 48 hours later both the irradiated and the opposite shielded leg were inoculated with a tissue suspension of spontaneous mammary carcinoma developed in Z female mice and maintained by serial transplantation in ZBC male mice. The inhibition of the growth of several different tumors inoculated into the irradiated leg was striking when compared with the tumor in the shielded leg. The tumor in the shielded leg grew at the same rate as tumors in nonirradiated control animals of the same age and strain. The present report deals with a study of the effect of different dose levels of pretransplantation irradiation (PTI). In this series of experiments the inoculation of tumor cells was limited to the irradiated site, thus allowing determination of the effect of PTI on the survival of the animals. A detailed study of the growth rate of tumors developing in both irradiated and nonirradiated tissues was carried out.