National Cancer Institute®
Last Modified: March 1, 2002
UI - 11840325
AU - Lasorella A; Uo T; Iavarone A
TI - Id proteins at the cross-road of development and cancer.
SO - Oncogene 2001 Dec 20;20(58):8326-33
AD - Department of Neurology, Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
A large body of evidence has been accumulated that demonstrates dominant effects of Id proteins on different aspects of cellular growth. Generally, constitutive expression of Id not only blocks cell differentiation but also drives proliferation. In some settings, it is sufficient to render cells immortal or induce oncogenic transformation. The participation of Id proteins in advanced human malignancy, where they are frequently deregulated, has been dramatically bolstered by the recent discovery that Id exert pivotal contributions to many of the essential alterations that collectively dictate malignant growth. Relentless proliferation associated with self-sufficiency in growth signals and insensitivity to growth inhibitory signals, sustained neoangiogenesis, tissue invasiveness and migration capabilities of tumor cells all share dependency on the unlimited availability of Id proteins. It is remarkable that many of these features recapitulate those physiologically propelled by Id proteins to support normal development. We propose that the participation of Id in multiple fundamental traits of cancer may be the basis for unprecedented therapeutic opportunities.
UI - 11792751
AU - Plath T; Peters M; Detjen K; Welzel M; von Marschall Z; Radke C;
TI - Wiedenmann B; Rosewicz S Overexpression of pRB in human pancreatic carcinoma cells: function in chemotherapy-induced apoptosis.
SO - J Natl Cancer Inst 2002 Jan 16;94(2):129-42
AD - T. Plath, M. Peters, K. Detjen, M. Welzel, Z. von Marschall, B. Wiedenmann, S. Rosewicz (Department of Hepatology and Gastroenterology), C. Radke (Department of Pathology), Charite, Campus Virchow-Klinikum, Humboldt-University, Berlin, Germany.
BACKGROUND: Human pancreatic adenocarcinomas are highly resistant to chemotherapy. The p16 tumor-suppressor protein is inactivated in more than 90% of human pancreatic cancers. The p16 protein transcriptionally inhibits expression of retinoblastoma tumor-suppressor gene pRB. The pRB protein transcriptionally inhibits expression of the p16 gene. Because pRB normally prevents apoptosis, we investigated whether pRB is involved in resistance to chemotherapy-induced apoptosis in pancreatic cancer cells. METHODS: pRB expression was examined by immunohistochemistry in 106 human pancreatic tissue specimens. The human pancreatic tumor cell line Capan-1 (pRB+/p16-) was stably transfected with p16 to functionally inactivate pRB. pRB gene expression was examined by western and northern blot analyses, and pRB function was assessed by electrophoretic mobility shift assays and promoter transactivation studies for the transcription factor E2F. Changes in cell sensitivity to chemotherapy were measured by assays for cytotoxicity and apoptosis. RESULTS: pRB was overexpressed in pancreatic ductal adenocarcinomas but was hardly detectable in other pancreatic malignancies, chronic pancreatitis, or nontransformed human pancreatic tissue. Expression of p16 in Capan-1 cells resulted in the loss of pRB gene and protein expression concomitant with increased activity of the transcription factor E2F, which was not detected in wild-type or control-transfected Capan-1 cells. Wild-type and control-transfected Capan-1 cells were resistant to chemotherapy-induced apoptosis, but pRB-depleted (i.e., p16-transfected) Capan-1 cells were highly sensitive. The effect was specific to pRB depletion because two other human pancreatic cancer cell lines that retained high pRB expression after p16 transfection were resistant to chemotherapy-induced apoptosis. CONCLUSIONS: Overexpression of pRB is associated with human pancreatic duct-cell cancer and may allow pancreatic cancer cells to evade chemotherapy-induced apoptosis.
UI - 11642725
AU - Cavallotti I; De Luca L; D'Aponte A; De Falco M; Acanfora F; Visciano
TI - ML; Gualdiero L; De Luca B; Baldi A; De Luca A Expression of the retinoblastoma-related p107 and Rb2/p130 genes in human placenta: an immunohistochemical study.
SO - Histol Histopathol 2001 Oct;16(4):1057-60
AD - Institute of Topographical Anatomy, School of Medicine, Second University of Naples, Italy.
It has been proposed that tumor suppressor genes may have a role in the mechanisms of proliferation and differentiation during human placental development. The Retinoblastoma gene family is a well known family of tumor suppressor genes. Many studies have pointed out a role of this family not only in cell cycle progression, but also during development and differentiation. On the light of these observations we have investigated the immunohistochemical expression pattern of the Retinoblastoma family members, p107 and Rb2/p130 in human placenta samples in first trimester and full-term placental sections. p107 and pRb2/p130 showed the most abundant expression levels during the first trimester of gestation and progressively declined to being barely detectable in the placenta by late gestation. These results indicate that the expression of the above genes is modulated during placental development and suggest a mechanism for controlling trophoblast proliferation.
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