Heterogeneity of guanylyl cyclase C expressed by human colorectal cancer cell lines in vitro.
Publication/Presentation Date
6-1-1998
Abstract
In humans, guanylyl cyclase C (GCC) is expressed by mucosal cells lining the intestine, from the duodenum to the rectum, but not by extraintestinal tissues. Expression of GCC persists after mucosal cells undergo neoplastic transformation, and this protein has been identified in all primary and metastatic colorectal tumors examined to date, suggesting that GCC may be a highly specific biomarker for colorectal cancer. The utility of GCC as a diagnostic biomarker and therapeutic target is predicated, in part, on defining the variability of its expression in colorectal cancer cells. Similarly, the utility of this biomarker to define tumor burden in diagnosing, staging, and postoperative surveillance of patients is predicated on quantifying GCC expression in cancer cells in tissues and blood. The present studies examined the heterogeneity of GCC expression in eight human colorectal carcinoma cell lines in vitro representing the full spectrum of cytological differentiation. Quantification of GCC expression by ligand binding and stimulation of cGMP accumulation demonstrated that functional GCC expression is heterogeneous in different colorectal cancer cell lines. Qualitative reverse transcription (RT)-PCR demonstrated that all colorectal cancer cells examined expressed GCC mRNA. However, GCC expression varied 100-fold in different colorectal cancer cell lines, determined by a novel quantitative RT-PCR assay. Functional and molecular expressions of GCC were unrelated to the differentiation state of cancer cells. These studies suggest that GCC is heterogeneously expressed by colorectal cancer cells in vitro and suggest a role for quantitative RT-PCR analysis in the development of diagnostic tests using GCC as a biomarker for metastatic colorectal cancer.
Volume
7
Issue
6
First Page
505
Last Page
514
ISSN
1055-9965
Published In/Presented At
Waldman, S. A., Barber, M., Pearlman, J., Park, J., George, R., & Parkinson, S. J. (1998). Heterogeneity of guanylyl cyclase C expressed by human colorectal cancer cell lines in vitro. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 7(6), 505–514.
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
9641495
Department(s)
Administration and Leadership
Document Type
Article