To determine the role of p27 in tumorigenesis, we examined its mutational status in 74 non-Hodgkin's lymphomas (NHLs) (52 of B-cell phenotype, 22 of T-cell phenotype), 5 lymphoma cell lines, and 42 adult T-cell leukemias/lymphomas (ATLs) using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and Southern blot analyses.
In contrast, absent or low p16, p21, and p27 immunostaining was observed in most HPV-negative cervical adenocarcinomas and might contribute to carcinogenesis in these tumors.
Here we identify pRb and p53 doubly deficient (DKO) prostate tumorigenesis as a context in which p27 ubiquitination by SCF<sup>Skp2/Cks1</sup> is required for p27 downregulation. p27 protein accumulated in prostate when p27T187A KI mice underwent DKO prostate tumorigenesis. p27T187A KI or Skp2 knockdown (KD) induced similar degrees of p27 protein accumulation in DKO prostate cells, and Skp2 KD did not further increase p27 protein in DKO prostate cells that contained p27T187A KI (AADKO prostate cells). p27T187A KI activated an E2F1-p73-apoptosis axis in DKO prostate tumorigenesis, slowed disease progression and significantly extended survival.
Collectively, these results demonstrate that SIRT1 suppression of p27 is required for KSHV-induced tumorigenesis and identify a potential therapeutic target for KS.
The cyclin-dependent kinase inhibitor p27(Kip1) (p27) plays a pivotal role in controlling cell proliferation during development and tumorigenesis. p27 has been implicated in pituitary tumorigenesis in studies of knockout mice and in analyses of human pituitary tumor samples.
We found miR-1307 was overexpressed in prostate cancer cells and tissues, overexpression of miR-1307 significantly promoted cell proliferation and tumorigenesis in vitro investigated by MTT assay, colony formation assay and soft agar growth assay, meanwhile overexpression of miR-1307 inhibited cell cycle inhibitors p21 and p27 both in mRNA and protein levels.
Concomitant knockdown of E6AP and p27 partially restores PC cell growth, supporting the contribution of p27 to the overall effect of E6AP on prostate tumorigenesis.
Our data indicate that p27 may be an important regulator of cellular proliferation in the anterior pituitary, the underexpression of which could play a role in pituitary tumorigenesis.
The results showed that p27, CDK6, and CCND1 played different roles in tumorigenesis and development, which are in accordance with CDK6 and CCND1 in affecting the cell cycle and cell proliferation. p27 regulated the cell cycle and inhibited cell proliferation by affecting formation of the cell cycle-dependent complex CDK6/CCND1, but did not directly affect the expression of CDK6 and CCND1.
To determine whether p27 alterations may be involved in tumorigenesis, we examined its mutational status in 36 primary breast carcinomas and 9 breast cancer cell lines using PCR-single-strand conformational polymorphism, direct DNA sequencing, and Southern blot analysis.
Urethane-induced lung tumors in mice frequently harbor mutations in the Kras oncogene, and in this study, we use this model to address the regulation of p27 during tumorigenesis.
To elucidate the importance of CDKI genes, including the p18 as well as the p16 and p27 genes in tumorigenesis of neuroblastoma, 25 neuroblastomas were analyzed for deletions by Southern blot analysis and for point mutations by polymerase chain reaction-single strand conformational polymorphism.