Gene activation in mammary cells

Hormonal Regulation of Breast Development and Activity

THE growth and differentiation of the mammary gland is controlled by the synergistic action of insulin, prolactin and ovarian or corticosteroid hormones1–4. The ovarian steroid induced alveolar development of the virgin mammary gland in vivo is mediated by activation of nucleic acid and protein synthesis and mitosis5–9. On the other hand, numerous studies using organ cultures, mostly of fragments of mid-pregnant mammary gland, emphasised the role of insulin as the mitogenic hormone in mammary gland development10–12. This variable nature of responsiveness of the mammary tissue to hormones in vivo and in organ culture has been discussed in recent reports13,14. The proliferative mammary gland of pregnancy, mostly used in these organ culture studies10–12, should contain a large proportion of cells in the division cycle at the time of excision; we considered that hormonal regulation of the fate of these dividing cells during incubation in vitro may influence the interpretation of the results obtained from the organ culture studies. In order to test this possibility, mid-pregnant mammary cells of Balb/c mice were labelled for 1 h with 3H-thymidine (3H-dT) in vivo, and the transit patterns of the labelled cells reaching mitosis were determined at different times in organ culture.

Role of insulin as a "permissive" hormone in mammary gland development.

Diabetes and pregnancy. A 21-year Swedish material.

SEXUAL differentiation of gonadotrophin secretion in the rat is known to occur during the early postnatal period under the action of testicular androgens1,2. Animals of either sex if exposed to androgen during this critical period develop the typical male pattern of gonadotrophin secretion after puberty with failure of ovulation, small polyfollicular ovaries lacking corpora lutea and a constant cornified vaginal epithelium. Several studies have localised this effect to the brain3,4 and more particularly to the anterior hypothalamus5, but very little is yet known of the mechanism of this effect.

Androgen-induced Sexual Differentiation of the Brain is Blocked by Inhibitors of DNA and RNA Synthesis

The acidic chromatin proteins extracted from normal and neoplastic mammary cells of C3H mice and Fischer rats have been compared by polyacrylamide gel electrophoresis, amino acid analysis, and radioactivity labeling patterns of synthesis in vitro . Following purification of chromatin from purified nuclei and extraction of histones in 2 m sodium chloride, the acidic proteins associated with DNA were subjected to electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate, and the stained gels were compared by absorbance scanning. Striking differences were observed in the banding patterns of proteins derived from the normal or neoplastic cells. Among a group of high-molecular-weight components characteristic of the lactational mammary gland, several were preserved while others were deficient or undetectable in the neoplastic cells. In addition, several components of intermediate molecular weight that were present in the neoplastic cells were undetectable in the normal pattern. Differences between the protein populations derived from normal and neoplastic cells were also demonstrated by amino acid analysis. Organ cultures of carcinoma and gland explants demonstrated that the normal mammary and gland synthesized lower-molecular-weight species at a higher net rate, whereas the carcinomas exhibited a relatively higher net rate of synthesis of high-molecular-weight components. 32P was incorporated as phosphoserine and phosphothreonine residues in the major portion of the proteins of all preparations, although the carcinomas exhibited a relatively lower net rate of phosphorylation of the high-molecularweight proteins. The differences between preparations derived from neoplastic and normal tissues could not be attributed merely to the physiological state of the gland, since the patterns of the proteins from the carcinomas were also significantly different from previous patterns derived from the mammary glands of virginal or pregnant animals. The results demonstrate that the neoplastic characteristics of mammary carcinomas are associated with an altered content and pattern of synthesis of acidic chromatin proteins.

Gene activation in mammary cells

Citations

Hormonal Regulation of Breast Development and Activity

Role of insulin as a "permissive" hormone in mammary gland development.

Diabetes and pregnancy. A 21-year Swedish material.

Androgen-induced Sexual Differentiation of the Brain is Blocked by Inhibitors of DNA and RNA Synthesis

Altered Populations of Acidic Chromatin Proteins in Breast Cancer Cells