The Regulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced Lung Tumor Promotion by Estradiol in Female A/J Mice

Abstract

Epidemiological studies indicate that women are at a higher risk developing lung cancer than men are. It is suggested that estrogen is one of the most important factors in lung cancer development in females. Additionally, cigarette smoke, and environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play salient roles in female lung carcinogenesis. However, the mechanisms responsible for the interaction of these factors in the promotion of lung cancer are still poorly understood. The present study was designed to explore two ideas: first, the synergistic lung tumorigenic effects of 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNK) combined with TCDD, 17β-estradiol (E2) or both through a long-term treatment experiment, and second, to identify early changes in the inflammatory and signaling pathways through short-term treatment experiments. The results indicate that A/J mice given E2 had strong effects in potentiating NNK-induced activation of MAPK signaling, NFκB, and COX-2 expression. In the long-term exposure model, E2 had a strong tumor promoting effect, whereas TCDD antagonized this effect in A/J mice. We conclude that treatment with NNK combined with either E2 or TCDD induces lung carcinogenesis and the promotion effects could be correlated with lung inflammation. E2 was shown to potentiate NNK-induced inflammation, cell proliferation, thereby leading to lung tumorigenesis.

Apoptosis in Colon Cancer (HT29) Cells Exposed to Estradiol Valerat

“…It is of interest that E concentrations were significantly lower in patients with recurrent ovarian cancer. [8] E2 was shown to potentiate NNK-induced inflammation, cell proliferation, thereby leading to lung tumorigenesis [9]. Thyroid cancer is also well coupled with estrogen.…”

Estrogen receptor alpha promotes smoking-carcinogen-induced lung carcinogenesis via cytochrome P450 1B1

“…In laboratory tests, the expression of ERa is increased in NSCLC [14], and ERα gene polymorphisms are associated with the risk of NSCLC [15]. In animal work, enhanced E2/ERα facilitates the smoking/NNK-induced lung tumorigenesis, whereas their inhibition significantly prevents this malignant process [16][17][18].…”