A MALDI-MS-based quantitative analytical method for endogenous estrone in human breast cancer cells

作者:Kim Kyoung Jin; Kim Hee Jin; Park Han Gyu; Hwang Cheol Hwan; Sung Changmin; Jang Kyoung Soon; Park Sung Hee; Kim Byung Gee; Lee Yoo Kyung; Yang Yung Hun; Jeong Jae Hyun*; Kim Yun Gon*
来源:Scientific Reports, 2016, 6(1): 24489.
DOI:10.1038/srep24489

摘要

The level of endogenous estrone, one of the three major naturally occurring estrogens, has a significant correlation with the incidence of post-menopausal breast cancer. However, it is challenging to quantitatively monitor it owing to its low abundance. Here, we develop a robust and highly sensitive mass-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based quantitative platform to identify the absolute quantities of endogenous estrones in a variety of clinical specimens. The one-step modification of endogenous estrone provided good linearity (R-2 > 0.99) and significantly increased the sensitivity of the platform (limit of quantitation: 11 fmol). In addition, we could identify the absolute amount of endogenous estrones in cells of the breast cancer cell line MCF-7 (34 fmol/10(6) cells) by using a deuterated estrone as an internal standard. Finally, by applying the MALDI-MS-based quantitative method to endogenous estrones, we successfully monitored changes in the metabolic expression level of estrones (17.7 fmol/10(6) letrozole-treated cells) in MCF-7 cells resulting from treatment with an aromatase inhibitor. Taken together, these results suggest that this MALDI-MS-based quantitative approach may be a general method for the targeted metabolomics of ketone-containing metabolites, which can reflect clinical conditions and pathogenic mechanisms.

  • 出版日期2016-4-19
  • 单位中国极地研究中心