Causation and Prevention of Solely Estrogen- Induced Oncogenesis: Similarities to Human Ductal Breast Cancer
Estrogens are intimately involved in the causation of some of the most prevalent cancers afflicting women, particularly, breast, endometrial, cervico-vaginal, and possibly ovarian. Therefore, it has become particularly pertinent to elucidate the molecular changes and mechanisms whereby estrogens elicit their oncogenic actions so that better prevention strategies can be developed. The estrogen-induced Syrian hamster tumors of the kidney have emerged as one of the most intensively studied in-vivo models in solely estrogen-induced oncogenesis. An advantage of this model is that the tumors occur in the absence of any intervening morphologic changes, but rather they are the result of the continuous progression of a subset of interstitial stem cells in the kidney leading to tumor formation. Evidence is presented that the origin of these tumors is derived from ectopic “uterine” stem cells, which are responsive to estrogenic hormones. The other animal tumor model studied is the highly sensitive estrogen-induced mammary tumors of female ACI rats. Their steroid receptor and other gene alterations have been delineated. Importantly, a crucial early event in this solely estrogen-induced oncogenic process, common to both animal tumor models, is the overexpression and amplification ofc-mycand its protein product. Chromosomal instability, in both early and large well-established frank tumors, is another important characteristic found during early E-induced oncogenesis. These features have been shown to be characteristic of human ductal carcinomasin-situand in primary invasive ductal breast carcinomas. The molecular alterations seen are considered crucial in eliciting estrogen-induced oncogenesis and have established for the first time a direct causal link between estrogen and the induction of chromosomal instability and aneuploidy in these estrogen-associated neoplasms.
KeywordsObesity Estrogen Hydrocarbon Polycyclic Aromatic Hydrocarbon Germinal
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