Abstract 311: Autophagic pathways and activity in breast and pancreatic cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 311
• Main Authors: Egilsson, Mar, Thoroddsen, Ulfur, Jonasson, Jon Gunnlaugur, Ogmundsdottir, Margret Helga, Ögmundsdottir, Helga M.
• Format: Journal Article
• Language: English
• Published: 01-10-2014
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-311

Autophagy is induced as a homeostatic process by energy shortage and cellular stress but can also be influenced by drugs. Poor autophagic function contributes to carcinogenesis but autophagy also promotes survival of tumours. We performed immunohistochemistry for LC3, pAMP kinase, p62, p53 on 15 samples from breast cancer and 14 from pancreatic cancer. P53 mutations were detected using CDGE. Autophagy was active (LC3 puncta in ≥ 30% of cells) in 5/15 breast carcinomas and 7/14 pancreatic carcinomas. This was associated with energy shortage (strong pAMP kinase expression) in 4/5 in breast samples and 5/7 in those from pancreas, often clearly colocalized when expression was variable. In contrast, activation of AMP kinase was not associated with autophagy in 4/8 breast and 2/7 pancreatic cancers. In 2/5 breast samples and 2/7 from pancreas impaired autophagic flux was suggested by absent cytoplasmic LC3 staining and strong expression of p62. Nuclear expression of p53 was seen in 10/15 breast cancer samples and of those 3 were mutated, 11/14 pancreas samples showed nuclear staining for p53, none mutated. Three out of 7 non-mutated p53-protein-positive breast cancers had low autophagy. Autophagy was thus often associated with energy shortage, can clearly also be induced by other pathways, but p53 appears not to be involved. Lack of autophagy in the presence of energy shortage suggests defects in induction. There is, therefore, considerable variability in autophagic pathways and activity in cancer and this will have to be taken into account when considering therapeutic intervention in the autophagic process.
Citation Format: Mar Egilsson, Ulfur Thoroddsen, Jon Gunnlaugur Jonasson, Margret Helga Ogmundsdottir, Helga M. Ögmundsdottir. Autophagic pathways and activity in breast and pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 311. doi:10.1158/1538-7445.AM2014-311