The role of apoptosis in gynaecological malignancies.
Apoptosis is a process of single-cell deletion requiring active participation of the cell in its own demise. First described in 1972, it is now known to play a major role in embryogenesis, tissue homeostasis and neoplasia. Apoptosis can be initiated when DNA damage occurs causing the cell to pause in its reproductive cycle. If the DNA damage is beyond repair, the cell proceeds to apoptotic cell death. When the genetic mechanism(s) involved in the pathway of apoptosis is altered, the cell does not die. Further mutations occur by proliferation and such multiple mutational events can lead to a malignant phenotype and cancer growth. The tumour suppressor gene p53 causes a DNA-damaged cell to rest and attempt repair. If damage is irreparable, p53 levels will continue to increase, initiating apoptosis. Mutation of p53, found in approximately 50% of cancers, can stop the apoptotic process. Increased bcl-2 expression, an apoptosis inhibitor, also plays a role in cellular transformation and cancer growth. Its altered expression occurs in the presence of oncogene expression. This paper reviews the role of apoptosis in malignant transformation, cancer growth, and response to therapy for gynaecological cancers. For cervical cancer and its precursors, data on apoptotic index, bcl-2 and Bax expression are presented and discussed in relationship to human papillomavirus expression. In ovarian epithelial malignancies, the role that apoptosis plays in chemotherapeutic responses is reviewed. The data for endometrial cancer are currently limited to apoptotic index.
Sheets
E E
EE
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, USA. eesheets@bics.bwh.harvard.edu
Yeh
J
J
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D015870:Gene Expression; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D008297:Male; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections; D014412:Tumor Virus Infections; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology