Kiguchi K, Iwamori M, Yamanouchi S, Ishiwata I, Saga M, Amemiya A
Department of Obstetrics and Gynecology, Toyoko Hospital, St. Marianna University School of Medicine, Kanagawa, Japan.
Clin Cancer Res. 1998 Dec;4(12):2985-90.
The expression of cholesterol sulfate (CS) is known to increase during squamous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the subsequent expression of transglutaminase-1 (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumorigenesis by CS, we examined the concentration and the potential for synthesis of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established from human uterine cervical cancer patients and compared them for the rate of expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expressed in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, cells derived from a keratinizing type of well-differentiated cervical carcinoma demonstrated strong potential for synthesis of CS, stained positive with anti-cytokeratin antibody, and exhibited a higher specific activity of TG-1, whereas the cells without CS did not stain positive with anti-cytokeratin antibody and exhibited a lower specific activity of TG-1. These findings indicate that CS is coexpressed with TG-1 and cytokeratin in the well-differentiated types of squamous cell cancers as a tumor marker.
已知硫酸胆固醇（CS）的表达在角质形成细胞的鳞状分化过程中会增加，并作为信号转导分子激活蛋白激酶C的ε、η和ζ形式，从而促进转谷氨酰胺酶-1（TG-1）和细胞角蛋白的后续表达。为了进一步深入了解CS对细胞分化和肿瘤发生的调控作用，我们分别检测了7例来自卵巢癌患者和4例来自子宫颈癌患者的手术标本，以及8种源自子宫颈癌患者的细胞系中CS的浓度和合成潜力，并比较了它们细胞角蛋白的表达率。CS存在于所有子宫颈癌组织标本中，但仅在卵巢癌组织标本中的黏液性囊腺癌中存在，并且细胞角蛋白在CS浓度高的组织中高表达，根据形态学检查这些组织被归类为高分化。同样，源自角化型高分化宫颈癌的细胞显示出很强的CS合成潜力，用抗细胞角蛋白抗体染色呈阳性，并且表现出较高的TG-1比活性，而没有CS的细胞用抗细胞角蛋白抗体染色不呈阳性，并且表现出较低的TG-1比活性。这些发现表明，在高分化类型的鳞状细胞癌中，CS作为一种肿瘤标志物与TG-1和细胞角蛋白共同表达。
