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Immuohistochemical and MALDI Imaging Reveal Changes in Expression and Phosphorylation of Annexin I and II in Chemical‐Induced Renal Tumors
Author(s) -
Leinweber Barbara,
Ma Ning,
Chacko Mary,
Everitt Jeffrey I,
Monks Terrence J.,
Lau Serrine S
Publication year - 2006
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.20.4.a66-a
Subject(s) - immunohistochemistry , tuberous sclerosis , cytoplasm , clear cell , cell growth , chemistry , microbiology and biotechnology , cell , cancer research , pathology , biology , medicine , biochemistry
2,3,5‐ Tris ‐(glutathion‐ S ‐yl)hydroquinone (TGHQ) is a nephrocarcinogen in the Eker rat, predisposed to renal tumors by a mutation in one allele (Tsc‐2 EK/+ ) of the tuberous sclerosis tumor suppressor, Tsc‐2, gene. In the present study, both Tsc‐2 +/+ (wild‐type) and Tsc‐2 EK/+ (mutant) rats were treated with TGHQ (i.p.) for 1–8 months. TGHQ induced cell proliferation in the kidney in the outer stripe of the outer medulla region in both Tsc‐2 +/+ and Tsc‐2 EK/+ rats, but only induced tumors in Tsc‐2 EK/+ rats. TGHQ increased transcription (cDNA microarray) and expression (immunohistochemistry, IHC) of annexin I and II (AI & AII) in injured cells (Tsc‐2 +/+ and Tsc‐2 EK/+ ) and preneoplastic lesions and renal tumors (Tsc‐2 EK/+ ). AII appeared in the cytoplasm in injured cells and the membrane in pre‐ and neoplastic cells, suggesting movement from the cytoplasm to membranes during compensatory proliferation following cell injury. MALDI‐TOF mass spectral imaging of rat kidney slices from a TGHQ treated (8 mo) Tsc‐2 EK/+ and an untreated Tsc‐2 +/+ rat revealed the same distribution of AI and II as seen with IHC. Moreover an increase in mono‐ and bisphosphorylated AI and AII were detected in TGHQ treated Tsc‐2 EK/+ rats by MS‐based tissue imaging technique. The role of native and post‐translationally modified AI and AII in TGHQ‐induced cell injury, cell proliferation and tumor formation is under investigation (GM39338, P30ES06694).