Role of Autophagy in Keratin Homeostasis in Breast Cancer
Annual summary rept. 1 Dec 2011-30 Nov 2012
UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEW BRUNSWICK
Pagination or Media Count:
Autophagy is an evolutionarily conserved catabolic process where the proteins and organelles of a cell are degraded using the lysosome. Defective autophagy has been implicated in mammary tumorigenesis as autophagy deficient beclin1- mice develop mammary hyperplasias at a higher frequency than their wild-type counterparts and beclin1 is monoallelically deleted in 40 of human breast tumors. PhosphoS73-K8, a modification required for keratin filament reorganization under stress, in autophagy-deficient cell lines, and mouse mammary tissues. We conclude that interfering with the phosphorylation of K8 at this residue however, does not appear to alter the reorganization of the keratin network under stress and therefore, are unable to investigate the role of this phosphorylation site in the context of autophagy deficiency. On the other hand, using gene expression analysis, we have identified increased Keratin 6 expression in autophagy-deficient cell lines, tumors generated from these cell lines and mouse mammary gland tissues. We are currently attempting to understand the association between of Keratin 6 expression and autophagy-deficiency in mammary tumorigenesis.
- Medicine and Medical Research