Oxyphenisatin acetate (NSC 59687) triggers a cell starvation response leading to autophagy, mitochondrial dysfunction, and autocrine TNFα-mediated apoptosis.

Oxyphenisatin (3,3-bis(4-hydroxyphenyl)-1H-indol-2-one) and several structurally related molecules have been shown to have in vitro and in vivo antiproliferative activity. This study aims to confirm and extend mechanistic studies by focusing on oxyphenisatin acetate (OXY, NSC 59687), the pro-drug of oxyphenisatin. Results confirm that OXY inhibits the growth of the breast cancer cell lines MCF7, T47D, HS578T, and MDA-MB-468.

The contribution of adhesion signaling to lactogenesis.

The mammary gland undergoes hormonally controlled cycles of pubertal maturation, pregnancy, lactation, and involution, and these processes rely on complex signaling mechanisms, many of which are controlled by cell-cell and cell-matrix adhesion. The adhesion of epithelial cells to the extracellular matrix initiates signaling mechanisms that have an impact on cell proliferation, survival, and differentiation throughout lactation. The control of integrin expression on the mammary epithelial cells, the composition of the extracellular matrix and the presence of secreted matricellular proteins all contribute to essential adhesion signaling during lactogenesis.

Connective Tissue Growth Factor (CTGF/CCN2) enhances lactogenic differentiation of mammary epithelial cells via integrin-mediated cell adhesion.

Background: Connective Tissue Growth Factor (CTGF/CCN2), a known matrix-associated protein, is required for the lactogenic differentiation of mouse mammary epithelial cells. An HC11 mammary epithelial cell line expressing CTGF/CCN2 was constructed to dissect the cellular responses to CTGF/CCN2 that contribute to this differentiation program.

Results: Tetracycline-regulated expression of CTGF/CCN2 in HC11 cells enhanced multiple markers of lactogenic differentiation including beta-casein transcription and mammosphere formation.

Mouse Mammary Epithelial Cells form Mammospheres During Lactogenic Differentiation.

A phenotypic measure commonly used to determine the degree of lactogenic differentiation in mouse mammary epithelial cell cultures is the formation of dome shaped cell structures referred to as mammospheres. The HC11 cell line has been employed as a model system for the study of regulation of mammary lactogenic differentiation both in vitro and in vivo. The HC11 cells differentiate and synthesize milk proteins in response to treatment with lactogenic hormones.

Global expression profiling reveals regulation of CTGF/CCN2 during lactogenic differentiation.

Mammary epithelial cells go through a series of developmental changes during pregnancy and lactation including proliferation, differentiation, secretion and apoptosis. HC11 mouse mammary epithelial cells, which undergo lactogen-induced differentiation in cell culture, were used to follow the changes in gene expression during this process. The expression profiles of over 20,000 genes were compared in HC11 cells undergoing lactogenic differentiation to non-differentiated cells using DNA microarray analysis.

Glucocorticoid induced expression of connective tissue growth factor contributes to lactogenic differentiation of mouse mammary epithelial cells.

The response of mammary epithelial cells to basement membrane and stroma induced signals contributes to the degree of differentiation in this tissue. The studies reported here indicate that connective tissue growth factor (CTGF) is highly elevated during lactogenic differentiation of the HC11 mouse mammary epithelial cell line. In addition, CTGF is expressed in the mouse mammary gland during pregnancy and lactation and it is expressed in primary mammary epithelial cell cultures established from pregnant mice.