The bone morphogenetic protein pathway is inactivated in the majority of sporadic colorectal cancers.

Background & Aims: The finding of bone morphogenetic protein (BMP) receptor 1a mutations in juvenile polyposis suggests that BMPs are important in colorectal cancer (CRC). We investigated the BMP pathway in sporadic CRC.

Methods: We investigated BMP receptor (BMPR) expression using immunoblotting and sequenced BMPR2 in CRC cell lines.

The bone morphogenetic protein pathway is active in human colon adenomas and inactivated in colorectal cancer.

Background: Transforming growth factor beta (TGFbeta) is important in colorectal cancer (CRC) progression. Bone morphogenetic proteins (BMPs), a subgroup within the TGFbeta superfamily, recently also have been implicated in CRC, but their precise role in CRC has yet to be investigated.

Methods: The authors used a tissue microarray and immunohistochemistry of BMP receptors and signal transduction elements in adenomas and CRC specimens to elucidate the role of BMP signaling in CRC carcinogenesis.

The effect of statins in colorectal cancer is mediated through the bone morphogenetic protein pathway.

Background & Aims: Epidemiological evidence suggests that statins prevent colorectal cancer (CRC), but the biological mechanism remains obscure. Statins induce bone morphogenetic protein (BMP) expression in bone cells. We have previously shown that BMPs act as tumor suppressors in CRC.

Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice.

Bone morphogenetic protein (BMP) signaling is known to suppress oncogenesis in the small and large intestine of mice and humans. We examined the role of Bmpr1a signaling in the stomach. On conditional inactivation of Bmpr1a, mice developed neoplastic lesions specifically in the squamocolumnar and gastrointestinal transition zones.

Tetrahydroxyquinone induces apoptosis of leukemia cells through diminished survival signaling.

Objective: Tetrahydroxyquinone is a molecule best known as a primitive anticataract drug but is also a highly redox active molecule that can take part in a redox cycle with semiquinone radicals, leading to the formation of reactive oxygen species (ROS). Its potential as an anticancer drug has not been investigated.

Methods: The effects of tetrahydroxyquinone on HL60 leukemia cells are investigated using fluorescein-activated cell sorting-dependent detection of phosphatidylserine exposure combined with 7-amino-actinomycin D exclusion, via Western blotting using phosphospecific antibodies, and by transfection of constitutively active protein kinase B.

Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation.

Wnt signaling defines the colonic epithelial progenitor cell phenotype, and mutations in the gene adenomatous polyposis coli (APC) that activate the Wnt pathway cause the familial adenomatous polyposis coli (FAP) syndrome and most sporadic colon cancers. The mechanisms that regulate the transition of epithelial precursor cells into their differentiated derivatives are poorly characterized. We report that Indian hedgehog (Ihh) is expressed by mature colonocytes and regulates their differentiation in vitro and in vivo.

Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon.

Background And Aims: The recent findings of bone morphogenetic protein (BMP) receptor Ia mutations in juvenile polyposis and frequent Smad4 mutations in colon cancer suggest a role for BMPs in the colonic epithelium and colon cancer. We investigated the role of BMP2 in the colon.

Methods: We assessed BMP receptor expression in cell lines using the reverse-transcribed polymerase chain reaction and immunoblotting.

Tumor suppressor pRB functions as a co-repressor of the CCAAT displacement protein (CDP/cut) to regulate cell cycle controlled histone H4 transcription.

The CCAAT displacement protein (CDP-cut/CUTL1/cux) performs a key proliferation-related function as the DNA binding subunit of the cell cycle controlled HiNF-D complex. HiNF-D interacts with all five classes (H1, H2A, H2B, H3, and H4) of the cell-cycle dependent histone genes, which are transcriptionally and coordinately activated at the G(1)/S phase transition independent of E2F. The tumor suppressor pRB/p105 is an intrinsic component of the HiNF-D complex.