The interaction between steroid hormones, human papillomavirus type 16, E6 oncogene expression, and cervical cancer.
Various risk factors have been implicated in the causation of cervical cancer including human papillomavirus (HPV), the early genes (E6 and E7 ) of which encode the main transforming proteins. Studies have suggested that steroid hormones may enhance the expression of these genes leading to loss of p53 gene-mediated cell apoptosis. A total of 120 cervical tissue samples were obtained from patients with proven cervical cancer. Patients who used depo-medroxyprogesterone acetate steroid contraception were recruited as part of the steroid arm. Only HPV DNA type 16 samples were used for the study. Controls included three cell lines (CaSki, SiHa, & C33A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal housekeeping gene. Of 120 patients, there were 111 patients with HPV type 16 identified. Of this number, RNA was present in 63 samples. There were 30 women (30/63) who used steroid contraception. In relation to patients who used contraception, HPV 16 E6 gene expression was present in 79% (n = 23) and 88% (n = 30) of steroid users compared to nonusers, respectively. In total there were 25 patients (40%) with expression of the HPV 16 E6*I gene and 30 patients with expression of the E6*II gene. There were 57% of steroid users (n = 17) who had expression of the E6*I/E6*II gene, compared to 52% (n = 17) of nonusers (P = 0.800). From a molecular level, this study does not confirm the role of injectable progesterones in cervical carcinogenesis.
Moodley
M
M
Department of Anatomical Pathology, Nelson R Mandela School of Medicine, Durban, South Africa. moodleym29@nu.ac.za
Sewart
S
S
Herrington
C S
CS
Chetty
R
R
Pegoraro
R
R
Moodley
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D003271:Contraceptive Agents, Female / Q000009:adverse effects* / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000096:biosynthesis*; D027383:Papillomaviridae / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000150:complications*; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology*
D003271:Contraceptive Agents, Female; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D017258:Medroxyprogesterone Acetate