SATB1 collaborates with loss of p16 in cellular transformation.

Tumor progression is associated with invasiveness and metastatic potential. The special AT-rich binding protein 1 (SATB1) has been identified as a key factor in the progression of breast cancer cells to a malignant phenotype and is associated with progression of human tumors. In normal development, SATB1 coordinates gene expression of progenitor cells by functioning as a genome organizer. In contrast to progenitor and tumor cells, SATB1 expression in nontransformed cells is not compatible with proliferation. Here we show that SATB1 expression in mouse embryonic fibroblasts induces cell cycle arrest and senescence that is associated with elevated p16 protein levels. Deletion of p16 overcomes the SATB1-induced senescence. We further provide evidence for an interaction of SATB1 with the retinoblastoma (RB)/E2F pathway downstream of p16. A combined deletion of the RB proteins, RB, p107 and p130 (triple-mutant; TM), prevents SATB1-induced G1 arrest, which is restored upon the reintroduction of RB into SATB1-expressing TM fibroblasts. SATB1 interacts with the E2F/RB complex and regulates the cyclin E promoter in an E2F-dependent manner. These findings demonstrate that p16 and the RB/E2F pathway are critical for SATB1-induced cell cycle arrest. In the absence of p16, SATB1 causes anchorage-independent growth and invasive phenotype in fibroblasts. Our data illustrate that p16 mutations collaborate with the oncogenic activity of SATB1. Consistent with our finding, a literature survey shows that deletion of p16 is generally associated with SATB1 expressing human cell lines and tumors.

Epidemiologic study and control of Taenia solium infections with praziquantel in a rural village of Mexico.

This study reports the results of an epidemiologic survey for the detection of Taenia solium in a rural village of 559 inhabitants in Sinaloa, Mexico, as well as a large scale treatment of the population with praziquantel. The study was carried out in two stages. In stage 1, serial stool analysis of 392 persons detected a cluster of three T. solium tapeworms. A fourth T. solium tapeworm was detected through a household census, giving a 1.32% prevalence rate for this helminth. Over 70% of the population over five years of age was treated with a 10 mg/kg dose of praziquantel, and no additional tapeworms were found. Environmental studies for the detection of Taenia sp. eggs in soil, water, and and objects from the houses of tapeworm-infected individuals showed only one soil sample containing eggs compatible with Taenia sp. A total of 72 domestic pigs were examined for the presence of cysticerci under the tongue. One animal had cysts, and belonged to a household that had two T. solium tapeworm infections. Stage 2 of the study was carried out one year after large scale antihelminthic treatment (LSAT), and no infections with Taenia sp. eggs were found. No cysticercus-infected pigs were detected. Intestinal parasitosis decreased from 69.2% to 37.5%. It is concluded that LSAT with praziquantel is efficient in decreasing endemic foci of T. solium. Seropositivity to T. solium bladder fluid antigens was tested by enzyme-linked immunosorbent assay and found to be 11% before LSAT and 7% one year later. In family members living with T. solium tapeworm carriers, the number of seropositive individuals was 28%. The relative risk ratio of seropositivity for persons living in the same household with a T. solium tapeworm carrier was 2.95. Positive response was significantly higher in the 30-39-year-old age group, in which 30% were seropositive in stage 1, compared with 7% one year after LSAT. High seropositivity rates were significantly associated with tapeworm clusters as well as with individuals with a clinical history of seizures.