Milgraum L Z, Witters L A, Pasternack G R, Kuhajda F P
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Clin Cancer Res. 1997 Nov;3(11):2115-20.
Expression of high levels of fatty acid synthase (FAS), an important enzyme in fatty acid synthesis, has been identified in a wide variety of human carcinomas. In breast and prostate carcinoma, FAS expression appears to be associated with aggressive disease. Recent biochemical studies have demonstrated that FAS expression in cancer cells connotes activation of the entire fatty acid synthesis pathway leading to the production of palmitic acid. Here, we explore the immunohistochemical expression of FAS and human acetyl-CoA carboxylase (HACC), the rate-limiting enzyme in fatty acid synthesis, in breast cancer progression from histologically normal breast through the development of in situ duct and lobular carcinoma to infiltrating carcinoma. Both FAS and the Mr 275,000 isoform of HACC are expressed in a small subset of cells in normal breast lobules and terminal ducts. Upon development of either in situ duct or lobular carcinoma, FAS and both isoforms of HACC are expressed at higher levels and in a majority of the cells. These findings suggest that expression of the enzymes of fatty acid synthesis are frequently altered early in the progression of human breast carcinoma.
脂肪酸合成中的一种重要酶——脂肪酸合酶（FAS），已在多种人类癌症中被证实有高水平表达。在乳腺癌和前列腺癌中，FAS表达似乎与侵袭性疾病相关。最近的生化研究表明，癌细胞中的FAS表达意味着整个脂肪酸合成途径被激活，从而导致棕榈酸的产生。在此，我们探究了FAS和人类乙酰辅酶A羧化酶（HACC，脂肪酸合成中的限速酶）在乳腺癌进展过程中的免疫组化表达情况，该过程包括从组织学正常的乳腺，经过原位导管癌和小叶癌的发展，直至浸润性癌。FAS和分子量为275,000的HACC同工型在正常乳腺小叶和终末导管的一小部分细胞中表达。在原位导管癌或小叶癌发生时，FAS和HACC的两种同工型均在大多数细胞中高表达。这些发现表明，在人类乳腺癌进展早期，脂肪酸合成酶的表达常常发生改变。
