Markers of squamous cell carcinoma in sarco/endoplasmic reticulum Ca2+ ATPase 2 heterozygote mice keratinocytes.
A mutation of Atp2a2 gene encoding the sarco/endoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) causes Darier's disease in human and null mutation in one copy of Atp2a2 leads to a high incidence of squamous cell tumor in a mouse model. In SERCA2 heterozygote (SERCA2(+/-)) mice keratinocytes, mechanisms involved in partial depletion of SERCA2 gene and its related tumor induction have not been studied. In this study, we investigated Ca(2+) signaling and differential gene expression in primary cultured keratinocytes from SERCA2(+/-) mice. SERCA2(+/-) keratinocytes showed reduced initial increases in intracellular concentration of calcium in response to ATP, a G-protein coupled receptor agonist, and higher store-operated Ca(2+) entry with the treatment of thapsigargin, an inhibitor of SERCA, compared to wild type kerationcytes. Protein expressions of plasma membrane Ca(2+) ATPases, NFATc1, phosphorylated ERK, JNK, and phospholipase gamma1 were increased in SERCA2(+/-) keratinocytes. Using the gene fishing system, we first found in SERCA2(+/-) keratinocytes that gene level of tumor-associated calcium signal transducer 1, crystalline alphaB, procollagen XVIII alpha1, and nuclear factor I-B were increased. Expression of involucrin, a marker of keratinocyte differentiation, was decreased in SERCA2(+/-) keratinocytes. These results suggest that the alterations of Ca(2+) signaling by SERCA2 haploinsufficiency alternate the gene expression of tumor induction and differentiation in keratinocytes.
Hong
Jeong Hee
JH
Department of Oral Biology, Brain Korea 21 Project, Oral Science Research Center, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea.
Yang
Yu-Mi
YM
Kim
Hyun Sil
HS
Lee
Syng-Ill
SI
Muallem
Shmuel
S
Shin
Dong Min
DM
D000818:Animals; D015415:Biomarkers; D020013:Calcium Signaling / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism*
D015415:Biomarkers; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases