bcl-2: role in epithelial differentiation and oncogenesis.
The precise regulation and maintenance of balance between cell proliferation and cell death in multicellular organisms is critical for tissue homeostasis. bcl-2 initiates a new gene family involved in the regulation of cell death and survival without affecting cell proliferation. Expression of Bcl-2 has been reported in a wide range of hematopoietic cells, nonneoplastic epithelia (both hormone-responsive and nonresponsive), and epithelial malignancies. Although the major group of epithelial cells expressing Bcl-2 protein are in the proliferating zones, expression is not directly related to cell proliferation. Bcl-2 is also associated with stem cells committed to differentiation and morphogenesis. The survival advantage provided by Bcl-2 prolongs the life span of epithelial cells with differentiation potential and allows proliferation, differentiation, and morphogenesis to proceed. The gene expression in hormone-responsive organs may contribute to the sustained life of those terminally differentiated epithelial cells and a decrease in Bcl-2 levels leads to cell death by apoptosis. Overexpression of bcl-2 protects epithelial cells from death, but it is neither able to immortalize normal cells, nor to cause tumorigenic transformation of immortalized epithelial cells. Heterogeneous expression of Bcl-2 in epithelial malignancies suggests that the gene is differentially regulated. Furthermore, its expression in association with precancerous lesions suggests a role in the early stage of tumorigenesis. The effects of Bcl-2 expression on sensitivity of epithelial cells to drug, radiation, and hormone therapies vary depending on the typed of tumor. Expression of Bcl-2 is associated with resistance to hormone therapy and recurrence in prostate carcinomas, whereas in lung and breast carcinomas it is associated with a better prognosis. Studies now being performed should clarify the underlying mechanisms of differential gene regulation in different tissues and show the clinical significance of the expression of bcl-2 and other members of the bcl-2 gene family.
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Department of Histopathology and Surgery, Royal Postgraduate Medical School/Hammersmith Hospital, London, UK.
Abel
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Foster
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Lalani
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D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009024:Morphogenesis; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2