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Tip60 Overexpression Exacerbates Chemotherapeutic Drug Treatment in Breast, Pancreatic, and Lung Cancer Cell Lines
Author(s) -
Ravichandran Priyadarshini,
Ginsburg Daniel
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.725.21
Subject(s) - cancer research , oncogene , cell cycle , biology , cell growth , nuclear localization sequence , apoptosis , cell culture , pancreatic cancer , cell , cancer , cytoplasm , microbiology and biotechnology , biochemistry , genetics
The Tip60 lysine acetyltransferase acetylates histones, p53 tumor suppressor, ATM kinase DNA repair enzyme, and androgen receptor transcription factor. Tip60 plays a vital role in transcription, DNA repair, and apoptosis. There is conflicting evidence that Tip60 may function as both a tumor suppressor and oncogene. We are interested in analyzing Tip60's role in breast, pancreatic, and lung carcinomas, and gauge into Tip60's potential as a therapeutic agent in these cancers. We hypothesize that due to Tip60's role in DNA repair and apoptosis, it serves as a tumor suppressor in these cancers. Therefore, overexpression of Tip60 should decrease proliferation in tumor cells and enhance the effects of chemotherapeutic agents. We have shown Tip60 levels in six different breast, pancreatic and lung cancer cell lines were significantly lower compared to non‐tumorigenic cells. While overexpression itself was found to reduce proliferation in only one cell line, Tip60 overexpression in addition to paclitaxel treatment, decreased proliferation 30‐60% more than administration of paclitaxel alone amongst the cancer cell lines. Moreover, we identified localization of Tip60 to be either in the cytoplasm or nucleus, and varied amongst the cell lines studied. Interestingly down‐regulation in cancer cells was associated with localization in the cytoplasm, thus, we cloned a nuclear localization sequence (NLS) into the Tip60 overexpression plasmid, and observed further decreases in proliferation than initially observed with the original plasmid. These results suggest that Tip60 serves as a tumor suppressor in breast, lung, and pancreatic cancers, consistent with previous data, and that Tip60 may also be useful as part of a cancer therapy in combination with currently used drugs.