Morphological characteristics of mitochondria in normal and malignant human breast epithelial cells correlate with estrogen and progesterone receptors: a stereological analysis

Abstract

The biological and pathological effects of estrogen and progesterone in hormone-sensitive breast tissue are due - on a molecular level - to estrogen and progesterone receptor signaling responses at the cell membrane, nucleus and mitochondria of breast epithelial cells. The present study focuses on the involvement of mitochondria in mammary gland carcinogenesis. Here we provide a quantitative comparison of mitochondria in normal vs. malignant human breast epithelial cells. Using stereological analysis, the volume (Vvm), surface (Svm), specific surface (Svm/Vvm) and numerical (Nvm) density of mitochondria were estimated for a total of 600 cells: 150 breast cancer cells positive for estrogen and progesterone receptors (group 1C); 150 breast cancer cells negative for estrogen and progesterone receptors (group 2C); and two compatible groups of 150 normal mammary epithelial cells (groups 1K and 2 K). Comparison of stereological parameters of mitochondria from complementary groups 1K and 1C shows that the surface, specific surface and numerical density of mitochondria is significantly reduced (p < 0.000) in cancer cells (1C). Comparison of complementary groups 2K and 2C shows that the numerical (p < 0.015) and specific surface (p < 0.000) density was significantly reduced, while the surface (p < 0.009) and volume density (p < 0.000) increased in cancerous cells (2C). Comparison of complementary groups 2K and 2C shows that the numerical (p < 0.015) and specific surface (p < 0.000) densities of the mitochondria were significantly reduced and the surface (p < 0.009) and volume density (p < 0.000) increased in cancerous cells (2C). Based on stereological analysis, we conclude that mitochondria in breast cancer cells are significantly different from mitochondria in normal cells in breast glandular epithelia. In addition, differences in mitochondria were observed which correlate with the presence/absence of estrogen and progesterone receptors.