Human chorionic gonadotropin decreases human breast cancer cell proliferation and promotes differentiation.

Human chorionic gonadotropin (hCG) is a glycoprotein produced by placental trophoblasts. Previous studies indicated that hCG could be responsible for the pregnancy-induced protection against breast cancer in women. It is reported that hCG decreases proliferation and invasion of breast cancer MCF-7 cells. Our research also demonstrates that hCG can reduce the proliferation of MCF-7 cells by downregulating the expression of proliferation markers, proliferating cell nuclear antigen (PCNA), and proliferation-related Ki-67 antigen (Ki-67). Interestingly, we find here that hCG elevates the state of cellular differentiation, as characterized by the upregulation of differentiation markers, ß-casein, cytokeratin-18 (CK-18), and E-cadherin. Inhibition of hCG secretion or luteinizing hormone/hCG receptors (LH/hCGRs) synthesis can weaken the effect of hCG on the induction of cell differentiation. Furthermore, hCG can suppress the expression of estrogen receptor alpha. hCG activated receptor-mediated cyclic adenosine monophosphate/protein kinase A signaling pathway. These findings indicated that a protective effect of hCG against breast cancer may be associated with its growth inhibitory and differentiation induction function in breast cancer cells.

Re-expression and epigenetic modification of maspin induced apoptosis in MCF-7 cells mediated by myocardin.

Breast cancer is the leading cause of cancer death in women worldwide. It is well known that oncogene activation and anti-oncogene inactivation affect the development and progression of breast cancer, but the role of oncogene activation and anti-oncogene inactivation in breast cancer is still not fully understood. We now report that maspin acts as a tumor suppressor gene to induce MCF-7 cell apoptosis. In addition, maspin promoter hypermethylation and histone hypoacetylation lead to silencing of maspin gene expression in MCF-7 cells. Moreover, DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-aza-dc) and/or the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) strongly up-regulated the expression of maspin in MCF-7 cells. Notably, myocardin can promote the re-expression of maspin in MCF-7 cells. Luciferase assay shows that myocardin activates the transcription of maspin promoter by CArG box. More importantly, 5-aza-dc/TSA and myocardin synergetically enhance re-expression of maspin and augment maspin-mediated apoptosis in MCF-7 cells. Thus, these data reveal the new insight that myocardin meditates apoptosis in breast cancer through affecting maspin re-expression and epigenetic modification to regulate the development of breast cancer, thereby raising the possibility of its use in breast cancer therapy.

Estrogen receptor α mediates proliferation of breast cancer MCF-7 cells via a p21/PCNA/E2F1-dependent pathway.

High expression of estrogen receptor α (ERα) is associated with a poor prognosis that correlates closely with cellular proliferation in breast cancer. However, the exact molecular mechanism by which ERα controls breast cancer cell proliferation is not clear. Here we report that ERα regulates the cell cycle by suppressing p53/p21 and up-regulating proliferating cell nuclear antigen (PCNA) and proliferation-related Ki-67 antigen (Ki-67) to promote proliferation of MCF-7 cells. In addition, 17-ß-estradiol (E2) enhances ERα-induced proliferation of MCF-7 cells by stimulating expression of PCNA and Ki-67. Knockdown of ERα significantly affects PCNA/Ki-67 and p53/p21 expression. Furthermore, ERα inhibits the transcriptional activity of p53/p21 in an estrogen response element-dependent manner. More importantly, we provide new evidence that ERα mediates proliferation of MCF-7 cells by up-regulating miR-17 to silence the expression of p21. Thus, these data provide new insights into the underlying effect of ERα on breast cancer proliferation.

The quantitative baseline HBsAg level as a predictor for therapeutic effect among HBeAg -positive chronic hepatitis B patients treated with PEG -IFN α-2b / 预防医学

Objective To evaluate the predictive effect of baseline hepatitis B surface antigen (HBsAg)on virological response in HBeAg -positive chronic hepatitis B patients treated with pegylated interferon (PEG -IFN ) α-2b. Methods The retrospective analysis compared the treatment efficacy of PEG -IFN α-2b in 55 cases of HBeAg -positive chronic hepatitis B patients with different baseline HBsAg levels.Serum HBV DNA load was measured at baseline and after 1 2,24,and 48 weeks of the therapy.Virological response was defined as HBV DNA <1 000 IU /ml.Serum HBsAg titers were quantitatively assayed at baseline,1 2 and 24 weeks.Results 1 8 patients had baseline HBsAg levels greater than 20 000 IU /ml(Group A),26 patients had baseline HBsAg levels between 1 500 and 20 000 IU /ml(Group B)and 1 1 patients had baseline HBsAg levels less than 1 500 IU /ml(Group C)after 48 weeks treatment with PEG -IFNα-2b.The achieved virological response rates of the three groups were 1 6.67%,42.31 % and 63.64% respectively with a statistically significant difference between group A and C (P <0.05).1 3 patients had HBsAg levels declined greater than 0.5 log1 0 and 30 patients had HBsAg levels declined less than 0.5 log1 0 at week 1 2 and the achieved virological response rates were 1 6.67%,46.2% and 33.3% respectively without statistically significant difference (P >0.05).1 6 patients with HBsAg <br> levels greater than 20 000 IU /ml after treatment of 24 weeks did not achieve virological response after treatment of 48 weeks.Conclusion Baseline HBsAg levels in combination with HBV DNA quantitative value may become an effective predictor for guiding optimal therapy with PEG -IFN α-2b against HBeAg -positive chronic hepatitis B.