Growth Control and Differentiation in Mammary Epithelial Cells

Abstract

Growth and differentiation of the mammary gland are controlled by various hormones and other environmental factors The role of hormones and growth factors in mammary development is discussed with regard to animal species, physiological stages, and the various experimental systems in vitro. In the female embryo, mammary morphogenesis is induced by the mesenchyme and is hormone independent, whereas androgens cause the partial necrosis of mammary epithelium in the male. Ductal growth during adolescence requires estrogen and prolactin or growth hormone. During pregnancy, progesterone participates in the development of the lobuloaveolar structure of the gland. After parturition, changes in the hormonal environment lead to production and secretion of milk. Proliferation and differentiation of mammary epithelium can be induced in culture systems. Insulin and epidermal growth factor (EGF) stimulate mammary cell proliferation in vitro. EGF is required for the optimal growth of the mammary gland during pregnancy. EGF also appears to play an important role in mammary tumorigenesis in certain mouse strains. Production of milk proteins can be induced in vitro by the synergistic interactions of prolactin, insulin, and glucocorticoids and is inhibited by EGF and progesterone. Complete or partial sequencing of several milk protein genes and comparative analysis have led to identification of a sequence of high homology and conservation in the 5 'flanking region that is likely to be involved in the regulation of milk protein gene expression.

Molecular Cloning and Characterization of the Murine Staf cDNA Encoding a Transcription Activating Factor for the Selenocysteine tRNA Gene in Mouse Mammary Gland

“…The binding activity of m-Staf in the mammary gland was undetectable at virgin and postlactating stages, when the gland is developmentally dormant. However, the binding activity increased markedly during the periods of pregnancy and lactation, when the mammary gland undergoes extensive growth and differentiation (36). Thus, the change in the m-Staf binding activity in the gland appears to be correlated to the developmental status of the mammary tissue.…”

“…Thus, the change in the m-Staf binding activity in the gland appears to be correlated to the developmental status of the mammary tissue. Because the development of the mammary gland is stimulated by various steroid and polypeptide hormones (36), the binding activity of m-Staf in the gland also may be hormonally regulated. In addition, we found that the level of tRNA sec in the mammary gland increased during pregnancy and lactation largely in parallel with that of m-Staf binding activity.…”

Knockdown of ICB-1 gene enhanced estrogen responsiveness of ovarian and breast cancer cells

“…Differentiation on the one hand and proliferation on the other hand are two basic cellular functions resulting from complex gene expression patterns being activated by specific signals. These functions are at least in part opposing, as differentiation processes often are associated with cell cycle arrest (Borellini & Oka 1989). Given that stimulation of cellular differentiation significantly enhances expression of ICB-1 (Treeck et al 1998(Treeck et al , 2002, which is an estrogen target gene, we hypothesized that knockdown of ICB-1 might also affect cellular proliferation.…”

Transforming growth factor alpha and mouse models of human breast cancer

“…TGFa is expressed and mitotically active in numerous breast cancer cell lines and has been directly implicated as a modulator of transformation in vivo (Borellini and Oka, 1989;Daniel and Silberstein, 1985;de Jong et al, 1998a;Salomon et al, 1984;Valverius et al, 1989). In fact, the discovery of TGFa was based on its ability to transform retrovirally-infected cultured ®broblasts (Todaro et al, 1980;de Larco and Todaro, 1978).…”