Soonmyoung Paik

Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland.

It has been suggested that environmental contaminants that mimic the effects of estrogen contribute to disruption of the reproductive systems of animals in the wild, and to the high incidence of hormone-related cancers and diseases in Western populations. Previous studies have shown that functionally, cadmium acts like steroidal estrogens in breast cancer cells as a result of its ability to form a high-affinity complex with the hormone binding domain of the estrogen receptor. The results of the present study show that cadmium also has potent estrogen-like activity in vivo. Exposure to cadmium increased uterine wet weight, promoted growth and development of the mammary glands and induced hormone-regulated genes in ovariectomized animals. In the uterus, the increase in wet weight was accompanied by proliferation of the endometrium and induction of progesterone receptor (PgR) and complement component C3. In the mammary gland, cadmium promoted an increase in the formation of side branches and alveolar buds and the induction of casein, whey acidic protein, PgR and C3. In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland.

Regulation of Human Breast Cancer by Secreted Growth Factors

Laboratory evidence is presented that estrogens are able to induce the production of numerous growth factors which can act in an autocrine or paracrine fashion in estrogen dependent breast cancer. Estrogen independent tumors can produce these same growth factors constitutively and so escape the need for estrogen stimulation. Growth inhibitory factors such as TGF-beta can also be controlled by estrogens and antiestrogens. It is unclear at present, however, how much of the cytostatic effect of antiestrogens in vivo is explained by the production of growth inhibitors. The overall control of breast cancer growth is mediated by the combined effects of these growth stimulatory and inhibitory factors in both breast stroma and epithelium. Interruption of the action of growth factors and the use of growth inhibitors may provide opportunities for new approaches to the treatment of breast cancer.

Clinical significance of erbB2 protein overexpression

Originally described as a homologue of the EGF receptor gene amplified in breast cancer [1], erbB-2 protein is now thought to be a cell membrane receptor for a newly described ligand-gp30 [2]. There is some confusion in the literature about the terminology for erbB-2. In brief, erbB-2, c-erbB-2, and HER-2 refer to the same human gene residing in the long arm of the chromosome 17, which has homology to human EGF receptor gene (c-erbB) [3]. erbB-2 protein, p185erbB-2, or p185HER-2 refer to the transmembrane receptor protein translated from the erbB-2 gene, which has a molecular weight of 185 kDa. c-neu refers to the rat counterpart of the erbB-2 gene [4].