BRCA1 inhibition of telomerase activity in cultured cells.

Telomerase, an enzyme that maintains telomere length, plays major roles in cellular immortalization and cancer progression. We found that an exogenous BRCA1 gene strongly inhibited telomerase enzymatic activity in human prostate and breast cancer cell lines and caused telomere shortening in cell lines expressing wild-type BRCA1 (wtBRCA1) but not a tumor-associated mutant BRCA1 (T300G). wtBRCA1 inhibited the expression of the catalytic subunit (telomerase reverse transcriptase [TERT]) but had no effect on the expression of a subset of other components of the telomerase holoenzyme or on the expression of c-Myc, a transcriptional activator of TERT. However, endogenous BRCA1 associated and partially colocalized with c-Myc; exogenous wtBRCA1 strongly suppressed TERT promoter activity in various cell lines. The TERT inhibition was due, in part, to suppression of c-Myc E-box-mediated transcriptional activity. Suppression of TERT promoter and c-Myc activity required the amino terminus of BRCA1 but not the carboxyl terminus. Finally, endogenous BRCA1 and c-Myc were detected on transfected mouse and human TERT promoter segments in vivo. We postulate that inhibition of telomerase may contribute to the BRCA1 tumor suppressor activity.

[Significance of human papillomavirus test in triage of patients with atypical squamous cell of undetermined significance].

OBJECTIVE: To investigate the significance of human papillomavirus test in triage of patients with atypical squamous cell of undetermined significance (ASCUS) diagnosed by cervical cytology. METHODS: Human papillomavirus test,colposcope and cervical biopsy were performed in 184 patients with a referral diagnosis of ASCUS by cervical cytology. RESULTS: Confirmed by pathological diagnosis of cervical biopsy, 112 cases were chronic inflammation (60.87%), 33 CIN I (17.93%), 17 CIN II (9.24%), 8 CIN III (4.35%), 4 cervical squamous carcinoma (2.17%) and 10 condyloma (5.43%). Of the 184 women with cytological ASCUS, 124 (67.39%) cases were positive in high-risk HPV test among which 66 cases were histologically confirmed as chronic inflammation (53.23%), 22 as CIN I (17.74%), 16 as CIN II (12.90%), 8 as CIN III (6.45%), 4 as cervical squamous carcinoma (3.23%) and 8 as condyloma (6.45%). The positive rate of HPV in groups of ASCUS were higher than those with negative HPV (P < 0.003). CONCLUSION: Women with ASCUS should be tested for HPV. Cervical biopsy under colposcopy is recommended for women with HR-HPV infection.

[Clinic value of combination of high-risk human papillomavirus test and cervical cytology test in diagnosing cervical lesions].

OBJECTIVE: To investigate the clinic value of combination of high-risk human papillomavirus test and cervical cytology test in diagnosis of cervical lesions. METHODS: Patients underwent physical examination at our department were checked by high-risk human papillomavirus test, cervical cytology test and colposcope from October 2004 to December 2006. Abnormal patients with cervical abnormalities were asked for pathological test.The diagnostic value of cervical lesions among these different methods were compared. RESULTS: Based on the criteria of histopathology, the sensitivity, specificity, positive-predictive value and negative-predictive value of high-risk human papillomavirus test for detecting all cases of CIN II and CIN III were 94.83%, 31.06%, 55.22% and 87.02% respectively, and those of the cervical cytology were 92.10%, 31.06%, 54.50% and 81.43% respectively.Those values changed to 99.65%, 18.55%, 61.46% and 97.62% respectively if two methods were combined. CONCLUSIONS: Human papillomavirus test and cervical cytology test combined with pathological test can improve the detective rate of cervical lesions and facilitate the treatment.