Abstract

Normal keratinocytes undergo differentiation in vitro in a manner regulated by calcium. Cytokines, tumor necrosis factor - alpha (TNF) and interferon- gamma (IFN) (which have receptors on keratinocytes), and the steroid hormone, 1,25 dihydroxy vitamin D3 [1,25(OH)2D], (which is produced by keratinocytes) promote the differentiation of normal keratinocytes, probably through calcium dependent mechanisms. Squamous carcinoma cell lines (SCC lines) show remarkable fidelity in their genotype to normal keratinocytes, but exhibit different degrees of differentiation in vitro. Some SCC lines remain in their proliferative stage of growth and cannot be induced to differentiate by calcium. In this proposal we address the question whether SCC lines respond to the prodifferentiating effect of 1,25(OH)2D, TNF and IFN, and whether the failure of SCC lines to differentiate normally is due to a defect in the calcium dependent intracellular molecular mechanisms by which these agents regulate differentiation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
2P01AR039448-06
Application #
3092416
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1988-07-15
Project End
1998-06-30
Budget Start
1993-08-20
Budget End
1994-06-30
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Bikle, Daniel D (2016) Extraskeletal actions of vitamin D. Ann N Y Acad Sci 1376:29-52
Bikle, Daniel D; Oda, Yuko; Tu, Chia-Ling et al. (2015) Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer. J Steroid Biochem Mol Biol 148:47-51
Bikle, Daniel D (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21:319-29
Bikle, Daniel D (2014) Vitamin D and cancer: the promise not yet fulfilled. Endocrine 46:29-38
Bikle, Daniel D (2014) The vitamin D receptor: a tumor suppressor in skin. Adv Exp Med Biol 810:282-302
Tu, Chia-Ling; Bikle, Daniel D (2013) Role of the calcium-sensing receptor in calcium regulation of epidermal differentiation and function. Best Pract Res Clin Endocrinol Metab 27:415-27
Jiang, Yan J; Kim, Peggy; Uchida, Yoshikazu et al. (2013) Ceramides stimulate caspase-14 expression in human keratinocytes. Exp Dermatol 22:113-8
Bikle, Daniel D (2012) Vitamin D and the skin: Physiology and pathophysiology. Rev Endocr Metab Disord 13:3-19
Bourguignon, L Y W; Earle, C; Wong, G et al. (2012) Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells. Oncogene 31:149-60
Tu, Chia-Ling; Crumrine, Debra A; Man, Mao-Qiang et al. (2012) Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. J Invest Dermatol 132:2350-2359

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