Psoriasin (S100A7) and calgranulin-B (S100A9) induction is dependent on reactive oxygen species and is downregulated by Bcl-2 and antioxidants

Carlsson, Hanna,1979Gothenburg University,Göteborgs universitet,Institutionen för kvinnors och barns hälsa,Institute for the Health of Women and Children (author)

S-100 proteins are calcium-binding proteins with important growth regulatory functions. Of these proteins, psoriasin and calgranulin-B have been shown to be highly upregulated in ductal carcinoma in situ (DCIS) of the breast and in psoriasis. The purpose of this study was to further elucidate the functional relevance of the overexpression of these two S-100 proteins in psoriasis and DCIS. We report the induction of both proteins by reactive oxygen species, phorbol ester TPA, and the induction of psoriasin in response to the PI3K inhibitor wortmannin. We also demonstrate that Bcl-2 overexpression represses the induction of psoriasin and calgranulin-B under these different conditions. The same effect was obtained with the antioxidant NAC, which indicates that the suppression of psoriasin and calgranulin-B induction is mediated by the antioxidant function of Bcl-2. Furthermore, we demonstrate that overexpression of a dominant negative IKKbeta also inhibits the induction of psoriasin suggesting that the NFkappaB pathway is involved in the induction of this protein. Also, we found NFkappaB responsive DNA elements in the upstream promoter region of psoriasin. MCF10A cells with a stable retroviral overexpression of psoriasin were significantly more resistant to H2O2-induced cell death than control cells further supporting the hypothesis that these S-100 proteins may play a role in oxidative stress response.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Dermatologi och venereologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Dermatology and Venereal Diseases hsv//eng
Acetylcysteine/pharmacology
Antioxidants/*pharmacology
Calcium-Binding Proteins/*biosynthesis/genetics
Calgranulin B/*biosynthesis/genetics
Cell Line
Cell Proliferation/drug effects
Cell Survival/drug effects
Down-Regulation
Epithelial Cells/drug effects
Humans
Keratinocytes/drug effects
Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism
Reactive Oxygen Species/*metabolism
Tumor Cells
Cultured

Yhr, Maria,1968Gothenburg University,Göteborgs universitet,Institutionen för kvinnors och barns hälsa,Institute for the Health of Women and Children(Swepub:gu)xyhrma (author)
Petersson, Stina,1981Gothenburg University,Göteborgs universitet,Institutionen för kvinnors och barns hälsa,Institute for the Health of Women and Children(Swepub:gu)xpetst (author)
Collins, N. (author)
Polyak, K. (author)
Enerbäck, Charlotta,1965Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för dermatologi och venereologi,Institutionen för kvinnors och barns hälsa,Institute of Selected Clinical Sciences, Department of Dermatology and Venereology,Institute for the Health of Women and Children(Swepub:gu)xenech (author)
Göteborgs universitetInstitutionen för kvinnors och barns hälsa (creator_code:org_t)

By the author/editor: Carlsson, Hanna, ...; Yhr, Maria, 1968; Petersson, Stina ...; Collins, N.; Polyak, K.; Enerbäck, Charlo ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Dermatology and ...

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