title: Inhibition of 4-nitroquinoline-1-oxide-induced oral carcinogenesis by dietary calcium.
abstract: Calcium is a strong inducer of keratinocyte differentiation. We have previously demonstrated that extracellular calcium promotes keratinocyte differentiation via E-cadherin-catenin complex-mediated phospholipase C-γ1 (PLC-γ1) activation in the plasma membrane. However, it is unclear whether dietary calcium regulates keratinocyte proliferation, differentiation or carcinogenesis. To address this issue, the rates of oral tumor and levels of proliferation and differentiation in the oral epithelium were assessed in mice on different calcium diets and the carcinogen 4-nitroquinoline-1-oxide. The results showed that mice on the high calcium diet had lower rates of oral tumors, lower levels of proliferation and higher levels of differentiation in the normal oral epithelium than those on the normal calcium diet. Higher levels of E-cadherin, β-catenin, p120-catenin (p120), epidermal growth factor receptor (EGFR), and calcium and lower levels of PLC-γ1 were also noted in the normal oral epithelium in mice on high calcium diet than the control mice. In contrast, mice on low calcium diet had opposite effects. However, dietary calcium had no effect on the proliferation, differentiation or the levels of E-cadherin, β-catenin, p120, PLC-γ1 and EGFR in oral tumors. These data indicate that dietary calcium increases calcium levels in oral epithelium, suppresses oral carcinogenesis, inhibits proliferation and promotes differentiation of normal oral epithelium. Increased E-cadherin, β-catenin, p120 and EGFR and decreased PLC-γ1 may participate in the inhibitory effect of dietary calcium in oral carcinogenesis.
authors.affiliation: Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China.
authors.forename: Chandrama
authors.initials: C
authors.lastname: Shrestha
authors.affiliation: Department of Pathology, The Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China.
authors.forename: Daiqiang
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pathology, The Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology, The Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Endocsrine Unit, Veterans Affairs Medical Center, Northern California Institute for Research and Education and University of California San Francisco, CA 94121, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Crumrine
authors.affiliation: Department of Pathology, Children's Hospital Los Angeles, University of Southern California Los Angeles, CA 90027, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China ; Endocsrine Unit, Veterans Affairs Medical Center, Northern California Institute for Research and Education and University of California San Francisco, CA 94121, USA.
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Xie
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000009:adverse effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002136:Calcium, Dietary / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation
chemical_list: D015415:Biomarkers; D002136:Calcium, Dietary; D015112:4-Nitroquinoline-1-oxide
keywords: Calcium; differentiation; oral carcinogenesis; proliferation