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Proliferation/inhibition markers following TPA in skin of exercised, calorie‐restricted mice
Author(s) -
Herndon Betty,
Jiang Yu,
Wasson Nicholas,
Xie Linglin,
Ouyang Ping,
Quinn Tim,
Wang Weiqun
Publication year - 2007
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.21.6.a926-c
Subject(s) - proliferating cell nuclear antigen , apoptosis , calorie restriction , downregulation and upregulation , cell growth , carcinogenesis , endocrinology , biology , medicine , leptin , cell cycle , cancer , biochemistry , gene , obesity
Carcinogenesis is a complex multi‐step process, resulting from genetic alterations leading to aberrant cellular proliferation. Caloric restriction is associated with resistance to this process in many species. To investigate the molecular level events underlying the interaction of diet, exercise and cancer resistance, this study assessed the expression of proliferation/inhibition markers in skin of TPA‐treated mice. 4 groups were pretreated 10 weeks: ad‐libitum‐fed, sedentary; exercised, pair fed with group a; ad‐libitum fed, exercised and 20% calorie restriction, sedentary. TPA was applied to shaved skin with tissue harvest 2 hr later. Skin sections were evaluated by IHC for: expression of proteins of cell proliferation (PCNA); a hormone regulator of energy expenditure (leptin); and an effector enzyme vital to apoptosis (caspase 3). Immunoreactivity was graded by cell counts and staining density. Skin PCNA was elevated in group “c” compared to all other groups, p<0.01. Caspase 3‐related apoptosis was elevated in group “b” (24 ± 2) vs. other groups (19 ± 2; 18 ±7; 18±10) but did not reach significance. Leptin staining was similar for all groups, p=0.97. We conclude that TPA‐treated mouse skin shows important upregulation of cell proliferation proteins after well‐fed exercise as expressed by PCNA. This protein is present throughout the cell cycle, and is involved in DNA repair. The elevated apoptotic marker, also in an exercised group, suggests the importance of metabolic studies to insight on aberrant cell death and proliferation. support: NIH R01CA106397, W.W.