PMID- 19020753
OWN - NLM
STAT- MEDLINE
DCOM- 20090202
LR  - 20151119
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 33
IP  - 6
DP  - 2008 Dec
TI  - Ectopic cyclin D1 overexpression increases chemosensitivity but not cell 
      proliferation in multiple myeloma.
PG  - 1201-13
AB  - We established a myeloma cell line (RPMI8226) with cyclin D1 overexpression in 
      which the transfected cyclin D1 gene was stably expressed. D1 transfectants 
      showed down-regulation of cyclin D2. Cell proliferation analysis did not show any 
      differences among RPMI8226, mock control, and D1 transfectants. The number of 
      S-phase cells increased while the number of G0/G1- and G2/M-phase cells decreased 
      in D1 transfectants, which indicates a prolonged S-phase caused by cyclin D1 
      transfection. A decreased number of G2/M-phase cells was also detected in myeloma 
      cells of patients with translocation t(11;14)(q13;q32). Western blot analysis 
      revealed an increase in the hyperphosphorylated form of retinoblastoma (Rb) 
      protein in D1 transfectants; however, the expression of p53, p16, Bax, Bad, 
      Bcl-2, and Mcl-1 did not significantly change. Treatment with anti-myeloma drugs 
      (melphalan, dexamethasone, bortezomib and immunomodulatory compounds) induced 
      apoptosis earlier in D1 transfectants compared with RPMI8226 and mock control via 
      the activation of both caspase-8 and -9. However, we could not detect a 
      relationship between cyclin D1 expression and the response to treatment with VAD 
      and bortezomib. Therefore, we assume that high sensitivity to anti-myeloma drugs 
      depends on the duration of the S-phase, but a clinical response might depend on 
      the number of myeloma cells with cyclin D1 overexpression.
FAU - Kuroda, Yoshiaki
AU  - Kuroda Y
AD  - Department of Hematology and Oncology, RIRBM, Hiroshima University, Minami-ku, 
      Hiroshima 734-8553, Japan.
FAU - Sakai, Akira
AU  - Sakai A
FAU - Tsuyama, Naohiro
AU  - Tsuyama N
FAU - Katayama, Yuta
AU  - Katayama Y
FAU - Munemasa, Shoso
AU  - Munemasa S
FAU - Asaoku, Hideki
AU  - Asaoku H
FAU - Okikawa, Yoshiko
AU  - Okikawa Y
FAU - Nakaju, Nanae
AU  - Nakaju N
FAU - Mizuno, Mami
AU  - Mizuno M
FAU - Ogawa, Katsunari
AU  - Ogawa K
FAU - Nishisaka, Takashi
AU  - Nishisaka T
FAU - Matsui, Hirotaka
AU  - Matsui H
FAU - Tanaka, Hideo
AU  - Tanaka H
FAU - Kimura, Akiro
AU  - Kimura A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (CCND1 protein, human)
RN  - 0 (CCND2 protein, human)
RN  - 0 (CDKN1B protein, human)
RN  - 0 (Cyclin D2)
RN  - 0 (Cyclins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Pyrazines)
RN  - 0 (Retinoblastoma Protein)
RN  - 136601-57-5 (Cyclin D1)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 5J49Q6B70F (Vincristine)
RN  - 69G8BD63PP (Bortezomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - Q41OR9510P (Melphalan)
SB  - IM
MH  - Aged
MH  - *Antineoplastic Agents/pharmacology/therapeutic use
MH  - Apoptosis/*drug effects
MH  - Boronic Acids/therapeutic use
MH  - Bortezomib
MH  - Cell Cycle/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Cyclin D1/genetics/*metabolism
MH  - Cyclin D2
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Cyclins/metabolism
MH  - Dexamethasone/pharmacology
MH  - Female
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Male
MH  - Melphalan/pharmacology
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/genetics/metabolism/pathology
MH  - Phosphorylation
MH  - Pyrazines/therapeutic use
MH  - Retinoblastoma Protein/metabolism
MH  - Thalidomide/pharmacology
MH  - Time Factors
MH  - Transfection
MH  - Up-Regulation
MH  - Vincristine/therapeutic use
EDAT- 2008/11/21 09:00
MHDA- 2009/02/03 09:00
CRDT- 2008/11/21 09:00
PHST- 2008/11/21 09:00 [pubmed]
PHST- 2009/02/03 09:00 [medline]
PHST- 2008/11/21 09:00 [entrez]
PST - ppublish
SO  - Int J Oncol. 2008 Dec;33(6):1201-13.