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Expression of Bcl-2 family member Bid in normal and malignant tissues
Maryla Krajewska1, Juan M Zapata, Ivo Meinhold-Heerlein
1The Burnham Institute, Program on Apoptosis and Cell Death Regulation, La Jolla, CA 92037, USA.
Abstract:
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.
Insights
Bid, a proapoptotic protein, is expressed in various normal human cells. Its altered expression in cancers correlates with patient survival and sensitivity to chemotherapy, suggesting a role in cancer treatment.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Bid is a unique Bcl-2 family member that activates proapoptotic proteins like Bax and Bak.
- Understanding Bid's expression is crucial for its role in apoptosis and cancer.
Purpose of the Study:
- To investigate Bid expression in normal human tissues and various cancers.
- To explore the correlation between Bid levels, clinical outcomes, and chemotherapy sensitivity.
Main Methods:
- Immunoblotting and immunohistochemistry were used to assess Bid expression.
- Analysis included normal tissues, human cancers (colon, ovarian, prostate, brain, lymphomas), and tumor cell lines.
- Clinical outcome and drug sensitivity data were correlated with Bid levels.
Main Results:
- Bid expression varied in normal tissues, notably in short-lived and apoptosis-sensitive cells.
- Altered Bid regulation was observed in some cancer types.
- Higher Bid levels correlated with longer recurrence-free survival in advanced prostate cancer.
- Elevated Bid levels in tumor cell lines predicted sensitivity to ribonucleotide reductase (RR)-inhibiting drugs.
Conclusions:
- Bid plays a role in apoptosis and its expression is altered in cancer.
- Bid levels may predict patient prognosis and response to specific chemotherapeutic agents.
- Further research into Bid's function in cancer is warranted.