Expression of the RAI gene is conducive to apoptosis: studies of induction and interference

TY - JOUR

T1 - Expression of the RAI gene is conducive to apoptosis: studies of induction and interference

AU - Laska, Magdalena J

AU - Strandbygård, Dorthe Jepsen

AU - Kjeldgaard, Anette

AU - Mains, Mette

AU - Corydon, Thomas J

AU - Memon, Ashfaque A

AU - Sørensen, Boe S

AU - Vogel, Ulla

AU - Jensen, Uffe Birk

AU - Nexø, Bjørn A

PY - 2007

Y1 - 2007

N2 - The RAI gene is also known as iASPP and PPP1R13L. Recent investigations have shown that the region encompassing RAI is important for the development of cancer in young and middle-aged persons. It has been speculated that the RAI product induces apoptosis by blocking NF-kappaB or inhibits apoptosis by blocking p53. Either way the gene could influence the survival of precancerous lesions. Here we report that the expression of RAI mRNA was increased in non-transformed lymphocytes and fibroblasts induced to undergo apoptosis by various means, such as treatment with etoposide, calcium ions, or interleukin-2 and/or serum deprivation. Treatment with etoposide increased the content of RAI protein, too, and caused it to translocate to the nucleus. Inhibition of RAI expression in lymphocytes and fibroblasts with siRNA reduced apoptosis, but treatment with the NF-kappaB-inhibiting substance sulfasalazine relieved this dependence. In the transformed cell line HEK-293 the association between RAI induction and apoptosis seemed broken. Thus, we hypothesize that RAI induction is necessary but not sufficient for apoptosis induction in non-transformed cells. Our results could be explained by a NF-kappaB mediated mechanism.

AB - The RAI gene is also known as iASPP and PPP1R13L. Recent investigations have shown that the region encompassing RAI is important for the development of cancer in young and middle-aged persons. It has been speculated that the RAI product induces apoptosis by blocking NF-kappaB or inhibits apoptosis by blocking p53. Either way the gene could influence the survival of precancerous lesions. Here we report that the expression of RAI mRNA was increased in non-transformed lymphocytes and fibroblasts induced to undergo apoptosis by various means, such as treatment with etoposide, calcium ions, or interleukin-2 and/or serum deprivation. Treatment with etoposide increased the content of RAI protein, too, and caused it to translocate to the nucleus. Inhibition of RAI expression in lymphocytes and fibroblasts with siRNA reduced apoptosis, but treatment with the NF-kappaB-inhibiting substance sulfasalazine relieved this dependence. In the transformed cell line HEK-293 the association between RAI induction and apoptosis seemed broken. Thus, we hypothesize that RAI induction is necessary but not sufficient for apoptosis induction in non-transformed cells. Our results could be explained by a NF-kappaB mediated mechanism.

KW - Apoptosis

KW - Cell Line

KW - Etoposide

KW - Flow Cytometry

KW - Gene Expression Regulation

KW - Herpes Simplex Virus Protein Vmw65

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Lymphocytes

KW - RNA Interference

KW - RNA, Messenger

KW - RNA, Small Interfering

KW - Sulfasalazine

KW - Time Factors

KW - Transfection

U2 - 10.1016/j.yexcr.2007.05.006

DO - 10.1016/j.yexcr.2007.05.006

M3 - Journal article

C2 - 17570360

SN - 0014-4827

VL - 313

SP - 2611

EP - 2621

JO - Experimental Cell Research

JF - Experimental Cell Research

IS - 12

ER -