Abstract
BackgroundEndogenous estrogens and estrogen metabolites play an important role in the pathogenesis and development of human breast, endometrial, and ovarian cancers. Increasing evidence also supports their involvement in the development of certain lung, colon and prostate cancers.MethodsIn this study we systemically surveyed endogenous estrogen and estrogen metabolite levels in each of the NCI-60 human tumor cell lines, which include human breast, central nerve system, colon, ovarian, prostate, kidney and non-small cell lung cancers, as well as melanomas and leukemia. The absolute abundances of these metabolites were measured using a liquid chromatography-tandem mass spectrometry method that has been previously utilized for biological fluids such as serum and urine.ResultsEndogenous estrogens and estrogen metabolites were found in all NCI-60 human tumor cell lines and some were substantially elevated and exceeded the levels found in well known estrogen-dependent and estrogen receptor-positive tumor cells such as MCF-7 and T-47D. While estrogens were expected to be present at high levels in cell lines representing the female reproductive system (that is, breast and ovarian), other cell lines, such as leukemia and colon, also contained very high levels of these steroid hormones. The leukemia cell line RMPI-8226 contained the highest levels of estrone (182.06 pg/106 cells) and 17β-estradiol (753.45 pg/106 cells). In comparison, the ovarian cancer cell line with the highest levels of these estrogens contained only 19.79 and 139.32 pg/106 cells of estrone and 17β-estradiol, respectively. The highest levels of estrone and 17β-estradiol in breast cancer cell lines were only 8.45 and 87.37 pg/106 cells in BT-549 and T-47D cells, respectively.ConclusionsThe data provided evidence for the presence of significant amounts of endogenous estrogens and estrogen metabolites in cell lines not commonly associated with these steroid hormones. This broad discovery of endogenous estrogens and estrogen metabolites in these cell lines suggest that several human tumors may be beneficially treated using endocrine therapy aimed at estrogen biosynthesis and estrogen-related signaling pathways.
Highlights
Endogenous estrogens and estrogen metabolites play an important role in the pathogenesis and development of human breast, endometrial, and ovarian cancers
The levels of endogenous estrogens and estrogen metabolite (EM) were measured in the NCI-60 cell lines, which comprise breast (n = 5), central nervous system (CNS) (n = 6), colon (n = 7), leukemia (n = 6), melanoma (n = 9), non-small cell lung (n = 9), ovarian (n = 9), prostate (n = 2), and renal (n = 8) cancers
This study utilized an liquid chromatography (LC)-tandem mass spectrometry (MS2) approach with the capability of measuring up to 15 different EMs to measure the levels of endogenous estrogens within the NCI-60 cell lines
Summary
Endogenous estrogens and estrogen metabolites play an important role in the pathogenesis and development of human breast, endometrial, and ovarian cancers. Increasing evidence supports their involvement in the development of certain lung, colon and prostate cancers. Endogenous estrogens and estrogen metabolites (EMs) have long been associated with carcinogenesis and development of several hormone-dependent human carcinomas, such as breast, endometrial, and ovarian cancers [1,2]. Increasing evidence suggests that these metabolites may be involved in the pathogenesis and development of human lung [3,4] and colon [5] cancers as well as prostate cancer [6]. The effects of E2 and other estrogens have expanded to include roles in neurological function [8], retinal degenerative disease [9], cardiovascular health [10], and even sleep regulation [11].
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