Regulation of Kallikrein 6 Gene Expression and Protein Secretion in Colon Cancer Model Systems
AuthorHenkhaus, Rebecca Sue
AdvisorIgnatenko, Natalia A.
Gerner, Eugene W.
Committee ChairIgnatenko, Natalia A.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractColon cancer occurs in over 150,000 men and women in the United States each year and is fatal about one third of the time. There are many well characterized genetic transformations which commonly occur during colon carcinogenesis, including mutations in the Adenometous Polyposis Coli (APC), Kirsten RAS (K-RAS) and p53 genes among many others. There are also many alterations in gene and protein expression which are not yet completely elucidated. We have identified kallikrein 6 (KLK6) as a gene whose expression is dependent on cancer associated proteins such as K-RAS, SRC and caveolin-1 (CAV-1). KLK6 is a member of the kallikrein protein family which consists of 15 secreted serine proteases. Like other types of proteases, kallikreins have been demonstrated to play a role in cancer progression and they hold promise as potential cancer biomarkers. The up-regulation of KLK6 was first identified by performing a microarray analysis on a mutant K-RAS transfected Caco2 cells. The activated K-RAS transfected cells expressed significantly more KLK6 than the mock transfected controls. Pathways downstream of K-RAS were found to induce KLK6 gene expression, including the p42/44 MAPK and the PI3-K/AKT pathways. Caveolae, plasma membrane associated structures, and their principle protein component, CAV-1, positively influence both KLK6 gene expression and KLK6 protein secretion in HCT116 colon cancer derived cells. Finally, it is shown that KLK6 increases the invasive potential of cells through laminin and Matrigel. Because KLK6 plays a role in cancer progression it may serves as a novel therapeutic target. Additionally, KLK6 holds potential for use as a serum biomarker for multiple types of cancer, including colon cancer for colon and other types of cancer.
Degree ProgramCancer Biology