Expression and characterization of an ASGP-1/ASGP-2 sialomucin complex in normal tissues
Date of Award
Doctor of Philosophy (Ph.D.)
Cell Biology and Anatomy
First Committee Member
Kermit Carraway, Committee Chair
Second Committee Member
Keith Brew, Committee Member
Mucins are high molecular weight glycoproteins which are extensively O-glycosylated on tandem repeats rich in serines and/or threonines. ASGP-1/ASGP-2 sialomucin complex (SMC) was originally discovered on the surface of a highly metastatic 13762 mammary adenocarcinoma where it is expressed as a heterodimer consisting of a mucinous subunit (ASGP-1) noncovalently associated with a transmembrane subunit (ASGP-2) containing two EGF-like domains. SMC is thought to serve as both an anti-recognition factor and a potential growth factor in 13762 ascites tumor cells. SMC has been characterized in mammary gland and colon where it is expressed at least partly as a soluble isoform which lacks the transmembrane and cytoplasmic domains. It has also been shown to be present in a number of other epithelial tissues. The expression, localization and characterization of SMC was investigated in rat airway, uterus and developing gastrointestinal (GI) tract. In the airway, SMC is expressed on the apical surface of the conducting epithelium with higher levels of expression occuring in more proximal passages. Airway SMC consists of both a soluble and membrane isoform. In the uterus, soluble and membrane isoforms are localized to the apical surface of the uterine eplthelium in virgin rats where SMC protein level cycles along with transcript during the estrous cycle. SMC expression is induced by estrogen and inhibited by progesterone in ovariectomized rats. In early pregnant rat, SMC is expressed until the time for blastocyst receptivity, when it is abruptly down-regulated. This down-regulation is prevented by the anti-progestin (RU486), and SMC expression is inversely correlated with implantation during receptivity. In the developing GI system SMC is first found on embryonic day 16 on the surface of nasal and buccal mucosa, salivary glands, and the gastroduodenal junction. During the first 2-3 postnatal weeks, expression is localized to the base of small intestine and colonic crypts. By the end of the fourth postnatal week, colonic expression changes to an adult pattern. These results suggest that SMC can serve numerous purposes in tissues including a protective agent in the airway, an anti-implantation factor in uterus and a potential growth factor in developing intestine.
Biology, Cell; Health Sciences, Oncology
Mcneer, Richard, "Expression and characterization of an ASGP-1/ASGP-2 sialomucin complex in normal tissues" (1997). Dissertations from ProQuest. 93.