PMID- 10086343
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 10
DP  - 1999 Mar 11
TI  - Involvement of retinoblastoma (Rb) and E2F transcription factors during
      photodynamic therapy of human epidermoid carcinoma cells A431.
PG  - 1891-6
AB  - Photodynamic therapy (PDT), a promising new therapeutic modality for the
      management of a variety of solid malignancies and many non-malignant diseases, is
      a bimodal therapy using a porphyrin based photosensitizing chemical and visible
      light. The proper understanding of the mechanism of PDT-mediated cancer cell-kill
      may result in improving the efficacy of this treatment modality. Earlier we have 
      shown (Proc. Natl. Acad. Sci. USA; 95: 6977-6982, 1998) that silicon
      phthalocyanine (Pc4)-PDT results in an induction of the cyclin kinase inhibitor
      WAF1/CIP1/p21 which, by inhibiting cyclins (E and D1) and cyclin dependent
      kinases (cdk2 and cdk6), results in a G0/G1-phase arrest followed by apoptosis in
      human epidermoid carcinoma cells A431. We have also demonstrated the generation
      of nitric oxide during PDT-mediated apoptosis (Cancer Res.; 58: 1785-1788, 1998).
      Retinoblastoma (pRb) and E2F family transcription factors are important proteins,
      which regulate the G1-->S transition in the cell cycle. Here, we provide evidence
      for the involvement of pRb-E2F/DP machinery as an important contributor of
      PDT-mediated cell cycle arrest and apoptosis. Western blot analysis demonstrated 
      a decrease in the hyper-phosphorylated form of pRb at 3, 6 and 12 h post-PDT with
      a relative increase in hypo-phosphorylated pRb. Western blot analysis also
      revealed that PDT-caused decrease in phosphorylation of pRb occurs at serine-780.
      The ELISA data demonstrated a time dependent accumulation of hypo-phosphorylated 
      pRb by PDT. This response was accompanied with down-regulation in the protein
      expression of all five E2F (1-5) family transcription factors, and their
      heterodimeric partners DP1 and DP2. These results suggest that Pc4-PDT of A431
      cells results in a down regulation of hyper-phosphorylated pRb protein with a
      relative increase in hypo-phosphorylated pRb that, in turn, compromises with the 
      availability of free E2F. We suggest that these events result in a stoppage of
      the cell cycle progression at G1-->S transition thereby leading to a G0/G1 phase 
      arrest and a subsequent apoptotic cell death. These data provide an evidence for 
      the involvement of pRb-E2F/DP machinery in PDT-mediated cell cycle arrest leading
      to apoptosis.
FAU - Ahmad, N
AU  - Ahmad N
AD  - Department of Dermatology, Case Western Reserve University, Cleveland, Ohio
      44106, USA.
FAU - Gupta, S
AU  - Gupta S
FAU - Mukhtar, H
AU  - Mukhtar H
LA  - eng
GR  - P01 CA 48735/CA/NCI NIH HHS/United States
GR  - P30 CA 43703/CA/NCI NIH HHS/United States
GR  - R01 CA51802/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F Transcription Factors)
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (E2F1 protein, human)
RN  - 0 (Retinoblastoma-Binding Protein 1)
RN  - 0 (TFDP1 protein, human)
RN  - 0 (Transcription Factor DP1)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/*metabolism
MH  - *Carrier Proteins
MH  - *Cell Cycle Proteins
MH  - *DNA-Binding Proteins
MH  - E2F Transcription Factors
MH  - E2F1 Transcription Factor
MH  - Humans
MH  - Phosphorylation
MH  - *Photochemotherapy
MH  - Rabbits
MH  - Retinoblastoma/*metabolism
MH  - Retinoblastoma-Binding Protein 1
MH  - Transcription Factor DP1
MH  - Transcription Factors/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 1999/03/23 00:00
MHDA- 1999/03/23 00:01
CRDT- 1999/03/23 00:00
PHST- 1999/03/23 00:00 [pubmed]
PHST- 1999/03/23 00:01 [medline]
PHST- 1999/03/23 00:00 [entrez]
AID - 10.1038/sj.onc.1202493 [doi]
PST - ppublish
SO  - Oncogene. 1999 Mar 11;18(10):1891-6. doi: 10.1038/sj.onc.1202493.