Telang N T, Axelrod D M, Bradlow H L, Osborne M P
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Ann N Y Acad Sci. 1990;586:70-8. doi: 10.1111/j.1749-6632.1990.tb17791.x.
The metabolism of E2 via the 16 alpha-hydroxylation pathway is reported to be elevated in breast cancer patients as well as in subjects at high risk for developing breast cancer. The biological relevance of the metabolic pathway during the initiational events that lead to the tumorigenic transformation of mammary epithelium is not fully understood. The results obtained from the in vitro experiments discussed in this report permit the following conclusions: 1. Human mammary TDLU, the presumptive target site for breast cancer, possesses metabolic competence to biotransform E2. 2. The biotransformation of E2 in TDLU via the 16 alpha-hydroxylation pathway is responsive to endogenous hormonal changes and to the presence of cancer, and is susceptible to carcinogenic insult. 3. The relative extent of E2 16 alpha-hydroxylation may constitute a sensitive metabolic marker for evaluating the susceptibility of noninvolved mammary epithelium to carcinogen-induced transformation.
据报道，在乳腺癌患者以及有患乳腺癌高风险的受试者中，通过16α-羟基化途径的E2代谢有所升高。导致乳腺上皮发生致瘤性转化的起始事件期间该代谢途径的生物学相关性尚未完全了解。本报告中讨论的体外实验结果得出以下结论：1. 人乳腺终末导管小叶单位（TDLU）是乳腺癌的假定靶位点，具有生物转化E2的代谢能力。2. TDLU中通过16α-羟基化途径的E2生物转化对内源性激素变化和癌症的存在有反应，并且易受致癌损伤。3. E2 16α-羟基化的相对程度可能构成一个敏感的代谢标志物，用于评估未受累乳腺上皮对致癌物诱导转化的易感性。
