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| Pten is essential for embryonic development and tumour suppression |
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| Author(s): Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP |
| Source: NATURE GENETICS Volume: 19 Issue: 4 Pages: 348-355 Published: AUG 1998 |
| Times Cited: 625 References: 44 |
| Abstract: The PTEN gene encodes a dual-specificity phosphatase mutated in a variety of human cancers. PTEN germline mutations are found in three related human autosomal dominant disorders, Cowden disease (CD), Lhermitte-Duclos disease (LDD) and Bannayan-Zonana syndrome (BZS), characterized by tumour susceptibility and developmental defects. To examine the role of PTEN in ontogenesis and tumour suppression, we disrupted mouse PTEN by homologous recombination. Pten inactivation resulted in early embryonic lethality. Pten(-/-) ES cells formed aberrant embryoid bodies and displayed an altered ability to differentiate into endodermal, ectodermal and mesodermal derivatives. Pten(+/-) mice and chimaeric mice derived from Pten(+/-) ES cells showed hyperplastic-dysplastic changes in the prostate, skin and colon, which are characteristic of to, LDD and BZS. They also spontaneously developed germ cell, gonadostromal, thyroid and colon tumours. In addition, Pten inactivation enhanced the ability of ES cells to generate tumours in nude and syngeneic mice, due to increased anchorage-independent growth and aberrant differentiation. These results support the notion that PTEN haploinsufficiency plays a causal role in Co, LDD and BZS pathogenesis, and demonstrate that Pten is a tumour suppressor essential for embryonic development. |
| Document Type: Article |
| Language: English |
| Reprint Address: Pandolfi, PP (reprint author), Mem Sloan Kettering Canc Ctr, Dept Human Genet, 1275 York Ave, New York, NY 10021 USA |
Addresses:
1. Mem Sloan Kettering Canc Ctr, Dept Human Genet, New York, NY 10021 USA
2. Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA
3. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 106AM |
| ISSN: 1061-4036 |
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