The tumor suppressor p16(INK4a) gene is a regulator of apoptosis induced by ultraviolet light and cisplatin.

p16(INK4a) (hereafter referred to as p16), a major cyclin-dependent kinase (CDK) inhibitor, is the product of a tumor-suppressor gene that has been found inactivated in different cancer types. In the present study, we sought to investigate the role of p16 in apoptosis induced by ultraviolet light (the most important etiological cause of skin cancer) and cisplatin (an anticancer DNA damaging agent). It is clearly shown that p16-compromised osteosarcoma U2OS cell line and p16-/- mouse embryo fibroblasts are sensitive to UV-induced apoptosis, as compared to their respective isogenic p16-expressing cells (EH1, EH2) and p16 +/+, indicating that p16 protects cells from undergoing apoptosis in response to UV light. Importantly, this reduction in UV-mediated apoptosis was associated with downregulation of the proapoptotic Bax protein, with no effect on Bcl-2 expression, suggesting that this antiapoptotic role of p16 is mediated via the intrinsic-mitochondrial pathway. On the other hand, p16 sensitized cells to cisplatin-mediated apoptosis through Bcl-2 decline. Interestingly, only proliferating but not G1-arrested EH1 cells underwent apoptosis in response to the anticancer drug. These novel findings provide further insight into the role of p16 in carcinogenesis, and has potential implications for future therapy strategies.

Value of flow cytometric assay for the detection of antisperm antibodies in women with a history of recurrent abortion.

PROBLEM: To verify the proposed relationship between recurrent spontaneous abortions and the presence of maternal antisperm antibodies (ASA) in women as detected by a sensitive and reliable method. METHOD OF STUDY: The presence of maternal antipaternal immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies were determined against three different paternal antigens comprising T, B lymphocytes and semen cells by a sensitive flow cytometric crossmatch method to examine their possible correlation with pregnancy outcome. Group 1 consisted of sera obtained from 24 women with a history of abortion, and lymphocytes and semen samples collected from their husbands at the same time of visiting the in vitro fertilization (IVF) Clinic at King Faisal Specialist Hospital and Research Center. Sera, lymphocytes and semen samples were also collected from six couples with no history of abortion who served as controls (Group 2). RESULTS: Using a sensitive flow cytometric assay to analyse the samples, without knowledge of clinical status, elevated levels of both IgG and IgM were detected in Group 1. However, no significant association was found when compared with normal females who had healthy pregnancies. CONCLUSION: Flow cytometry is a highly sensitive and specific tool for the detection of alloantibodies in human sera from patients with rejected transplanted organs. Our findings suggest that maternal antipaternal antibodies with respect to IgG and IgM classes do not play a major role in women with a history of recurrent abortions, despite the presence of increased levels of antibodies against three different sources of paternal antigens.