Elucidation of the relationship of BNIP3 expression to gemcitabine chemosensitivity and prognosis.
OBJECTIVE
To evaluate the significance of BNIP3 in the pathogenesis of pancreatic cancer, we analyzed the relationship between the expression of BNIP3 and survival rate of the patients with pancreatic cancer, or chemosensitivities in pancreatic cancer cell lines, particularly for gemcitabine, the first-line anti-tumor drug for pancreatic cancer.


METHODS
To compare the expression level of BNIP3 with the resistance to gemcitabine, eight pancreatic cancer cell lines were subjected to gemcitabine treatment and the quantitative real-time RT-PCR method was used to evaluate BNIP3 expression. Immunohistochemical analysis was also performed using 22 pancreatic cancer specimens to study relationship between BNIP3 expression and survival rate.


RESULTS
Although no significantly positive association between BNIP3 mRNA level and gemcitabine chemosensitivity was observed, pancreatic cancer cell lines that were sensitive to gemcitabine treatment tended to show high levels of BNIP3 expression. The converse, an absence of BNIP3 expression, was not correlated with gemcitabine resistance. We further compared the BNIP3 expression profiles of resected primary pancreatic cancer specimens with the prognosis of the patients, and found a tendency of favorable prognosis and low BNIP3 expression.


CONCLUSIONS
High levels of BNIP3 expression cannot be used as one of the predicting factors for gemcitabine chemosensitivity, and some yet to be known factors will have to fill the gap for the accurate prediction of pancreatic cancer chemosensitivity to gemcitabine. However, BNIP3 expression may have an impact on prediction of prognosis of patients with pancreatic cancer.
Ishida
Masaharu
M
Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Sendai, Japan.
Sunamura
Makoto
M
Furukawa
Toru
T
Akada
Masanori
M
Fujimura
Hiroko
H
Shibuya
Emiko
E
Egawa
Shinichi
S
Unno
Michiaki
M
Horii
Akira
A
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; C090121:BNIP3 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D003841:Deoxycytidine; D000093542:Gemcitabine