Koistinen Hannu, Seppälä Markku, Nagy Balint, Tapper Johanna, Knuutila Sakari, Koistinen Riitta
Department of Clinical Chemistry, Helsinki University Central Hospital, Biomedicum, Helsinki, Finland.
Am J Obstet Gynecol. 2005 Dec;193(6):1955-60. doi: 10.1016/j.ajog.2005.05.073.
Glycodelin is a major secretory glycoprotein of differentiated endometrial epithelium, rarely expressed in proliferative endometrium or endometrial cancer. We aimed to elucidate its role in growth and gene expression of endometrial adenocarcinoma cells, and hypothesized that glycodelin affects cell growth and tumor-associated gene expression.
Endometrial adenocarcinoma HEC-1B cells were transfected with glycodelin cDNA in both antisense and sense orientations. Cellular morphology, cell proliferation, and gene expression were compared between native and transfected cells.
Compared with native and antisense-transfected carcinoma cells, sense-transfected, glycodelin-producing carcinoma cells showed reduced proliferation, morphologic changes, and altered expression of cancer-related genes. Notably, anti-apoptotic Bcl-XL and MUC1 genes were down-regulated.
Reduction by glycodelin transfection of carcinoma cell proliferation and expression of MUC1 and Bcl-XL is significant because these genes are often overexpressed in human cancers--MUC1 is linked to invasive growth and metastases, and both confer resistance to chemotherapy. These results suggest a novel mechanism whereby malignant growth of endometrial adenocarcinoma cells is regulated.
糖蛋白14是分化型子宫内膜上皮的一种主要分泌性糖蛋白,在增殖期子宫内膜或子宫内膜癌中很少表达。我们旨在阐明其在子宫内膜腺癌细胞生长和基因表达中的作用,并假设糖蛋白14会影响细胞生长和肿瘤相关基因表达。
将糖蛋白14 cDNA以反义方向和正义方向转染子宫内膜腺癌HEC-1B细胞。比较天然细胞和转染细胞之间的细胞形态、细胞增殖和基因表达。
与天然细胞和反义转染的癌细胞相比,正义转染的、产生糖蛋白14的癌细胞增殖减少、形态改变且癌症相关基因表达改变。值得注意的是,抗凋亡基因Bcl-XL和MUC1基因下调。
糖蛋白14转染使腺癌细胞增殖以及MUC1和Bcl-XL表达降低具有重要意义,因为这些基因在人类癌症中常常过度表达——MUC1与侵袭性生长和转移有关,二者均赋予对化疗的抗性。这些结果提示了一种调控子宫内膜腺癌细胞恶性生长的新机制。