PMID- 20217131
OWN - NLM
STAT- MEDLINE
DCOM- 20101027
LR  - 20220310
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Print)
IS  - 0171-5216 (Linking)
VI  - 136
IP  - 11
DP  - 2010 Nov
TI  - Expression and significance of hypoxia-inducible factor-1 alpha and 
      MDR1/P-glycoprotein in human colon carcinoma tissue and cells.
PG  - 1697-707
LID - 10.1007/s00432-010-0828-5 [doi]
AB  - PURPOSE: Hypoxia in tumors is generally associated with chemoresistance and 
      radioresistance. However, the correlation between the heterodimeric 
      hypoxia-inducible factor-1 (HIF-1) and the multidrug resistance (MDR1) 
      gene/transporter P-glycoprotein (P-gp) has not been clearly investigated. This 
      study aims at examining the expression levels of HIF-1alpha and MDR1/P-gp in human 
      colon carcinoma tissues and cell lines (HCT-116, HT-29, LoVo, and SW480) and 
      ascertaining whether HIF-1alpha plays an important role in tumor multidrug resistance 
      with MDR1/P-gp. METHODS: The expression and distribution of HIF-1alpha and P-gp 
      proteins were detected in human colon carcinoma tissues and cell lines by 
      immunohistochemistry and immunocytochemistry using streptavidin/peroxidase (SP) 
      and double-label immunofluorescence methods. HIF-1alpha and MDR1 mRNA expression 
      levels in cell lines were analyzed using RT-PCR under normoxic and hypoxic 
      conditions, respectively. RESULTS: The immunohistochemical method shows that 
      HIF-1alpha and P-gp expression were not correlated with gender, age, location, and 
      differentiation degree (P > 0.05). However, the expression of HIF-1alpha and P-gp at 
      different Dukes' stages and whether involved in lymphatic invasion shows a 
      significant difference (P < 0.05). Correlation analysis displays that HIF-1alpha 
      protein expression was correlated significantly with P-gp expression (P < 0.01). 
      Double-label immunofluorescence demonstrates that coexpression of HIF-1alpha and P-gp 
      does exist in human colon carcinoma tissues. The mRNA expression of HIF-1alpha and 
      MDR1 was detected in the four human colon carcinoma cell lines under both 
      normoxia and hypoxia. Optical density values representing mRNA expression levels 
      of HIF-1alpha and MDR1 were found to be significantly higher in the same type cells 
      under hypoxic conditions than that under normoxic conditions, respectively 
      (P < 0.01). However, no significant differences of HIF-1alpha or MDR1 mRNA expression 
      were found among these cell lines, which exposed under the same PaO(2) cultural 
      conditions (P > 0.05). And the immunocytochemistry results were corresponding 
      with the analysis of mRNA expression. CONCLUSIONS: These results suggest that 
      hypoxia induce the expression of HIF-1alpha and MDR1/P-gp in colon carcinoma and 
      HIF-1alpha expression may be associated with the gene MDR1 (P-gp) and interactively 
      involved in the occurrence of tumor multidrug resistance.
FAU - Ding, Zhenyu
AU  - Ding Z
AD  - Department of Oncology, Southwest Hospital, Third Military Medical University, 30 
      Gaotanyan Street, Shapingba District, Chongqing 400038, China.
FAU - Yang, Li
AU  - Yang L
FAU - Xie, Xiaodong
AU  - Xie X
FAU - Xie, Fangwei
AU  - Xie F
FAU - Pan, Feng
AU  - Pan F
FAU - Li, Jianjun
AU  - Li J
FAU - He, Jianming
AU  - He J
FAU - Liang, Houjie
AU  - Liang H
LA  - eng
PT  - Journal Article
DEP - 20100309
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (ABCB1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (DNA Primers)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/*genetics
MH  - Aged
MH  - Cell Differentiation
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*genetics/pathology
MH  - DNA Primers
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2944968
EDAT- 2010/03/11 06:00
MHDA- 2010/10/28 06:00
PMCR- 2010/03/09
CRDT- 2010/03/11 06:00
PHST- 2009/01/31 00:00 [received]
PHST- 2010/02/08 00:00 [accepted]
PHST- 2010/03/11 06:00 [entrez]
PHST- 2010/03/11 06:00 [pubmed]
PHST- 2010/10/28 06:00 [medline]
PHST- 2010/03/09 00:00 [pmc-release]
AID - 828 [pii]
AID - 10.1007/s00432-010-0828-5 [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2010 Nov;136(11):1697-707. doi: 
      10.1007/s00432-010-0828-5. Epub 2010 Mar 9.