Expression of Bcl-2 family member Bid in normal and malignant tissues.
Bid is the only known Bcl-2 family member that can function as an agonist of proapoptotic Bcl-2-related proteins such as Bax and Bak. Expression of the proapoptotic Bcl-2 family protein Bid was assessed by immunoblotting and immunohistochemical methods in normal murine and human tissues, and in several types of human cancers and tumor cell lines. Bid expression in normal tissues varied widely, with prominent Bid immunostaining occurring in several types of short-lived cells (e.g., germinal center B cells, peripheral blood granulocytes, differentiated keratinocytes) and in apoptosis-sensitive cells (e.g., adult neurons). Analysis of Bid expression by immunostaining of 100 colon, 95 ovarian, and 254 prostate cancers, as well as 59 brain tumors and 50 lymphomas, revealed evidence of altered Bid regulation in some types of cancers. Correlations with clinical outcome data revealed association of higher levels of Bid with longer recurrence-free survival in men with locally advanced (T3 stage) prostate cancer (P=0.04). Immunoblot analysis of Bid protein levels in the NCI's panel of 60 human tumor cell lines revealed a correlation between higher levels of Bid and sensitivity to ribonucleotide reductase (RR)-inhibiting drugs (P<0.0005). Overexpression of Bid in a model tumor cell line by gene transfection resulted in increased sensitivity to apoptosis induction by a RR inhibitor. Taken together, these observations suggest a potential role for Bid in tumor responses to specific chemotherapeutic drugs, and lay a foundation for future investigations of this member of the Bcl-2 family in healthy and diseased tissues.
Krajewska
Maryla
M
The Burnham Institute, Program on Apoptosis and Cell Death Regulation, La Jolla, CA 92037, USA.
Zapata
Juan M
JM
Meinhold-Heerlein
Ivo
I
Hedayat
Hirad
H
Monks
Anne
A
Bettendorf
Herta
H
Shabaik
Ahmed
A
Bubendorf
Lukas
L
Kallioniemi
Olli-P
OP
Kim
Hoguen
H
Reifenberger
Guido
G
Reed
John C
JC
Krajewski
Stanislaw
S
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011817:Rabbits; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C494815:Bid protein, mouse; D002352:Carrier Proteins; D019253:Proto-Oncogene Proteins c-bcl-2