生物谷报道：由在McGill大学癌症中心Michel L. Tremblay领导的团队，在五名感染乳腺癌的妇女的两名妇女中已经发现一个基因在乳腺癌传播中扮演的角色。他们的刊登在《自然遗传杂志上》研究，显示了在小鼠中这个基因活性的不完善可以使癌症增长减缓并且在某些情况下阻止肿瘤的发生。
McGill癌症研究中心主任Michel L. Tremblay医生说，“我们鉴定的这个基因是PTP1b，我们已经知道它在糖尿病和肥胖症扮演的角色。”“在这项新的研究中，我们发现PTP1b在调节代谢重的角色是相当关键的，它可以促进癌症肿瘤的增殖和转移.”同样来自这个组织重的研究者在1999年《科学》杂志发表的另一篇文章显示了抑制PTP1b基因产生的酶活性可以治疗二期糖尿病和肥胖疾病。很多大型制药公司因此开发了对于这些疾病的新抑制剂。
Tremblay总结到，“尽管这项研究是在小鼠中使用简单的基因和药理学确证，我们知道所有乳腺癌例子中的30％～40％都包含PTP1b基因的过度表达--这在某些情况下要超过遗传学观点所占的比例。”
Figure 1. Reduced rate of tumor development, number of tumors and lung metastases in NDL2 Ptpn1-/- mice.
(a) Kaplan-Meier kinetic analysis of tumor occurrence in NDL2 Ptpn1 female transgenic mice. In order to detect mammary tumors, mice were examined twice per week after weaning of the second litter. The curves were drawn and analyzed using Prism software. Log rank tests of survival plots of the data indicated a statistically significant difference between each survival curve: NDL2 Ptpn1+/+ versus NDL2 Ptpn1+/- (P = 0.004); NDL2 Ptpn1+/+ versus NDL2 Ptpn1-/- (P = 0.0001); and NDL2 Ptpn1+/- versus NDL2 Ptpn1-/- (P = 0.001). The number of animals analyzed for each genotype (n) and the median time to tumor onset (T50) are also shown. (b) Female mice described in a were killed at different time points (0.3, 4 or 6 weeks) after tumor initiation, and the number of tumors was determined (mean s.d.). Numbers in parentheses represent the number of mice per group. (c) Lung metastases were monitored by histopathological analysis from hematoxylin and eosin–stained lung sections from all animals presented in a. Numbers in parentheses represent the frequency of lung metastases
原文出处：
Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis
Sofi G Julien, Nadia Dubé, Michelle Read, Janice Penney, Marilene Paquet, Yongxin Han, Brian P Kennedy, William J Muller & Michel L Tremblay
Published online: 28 January 2007 | doi:10.1038/ng1963
Abstract | Full text | PDF (531K) | Supplementary Information
作者简介：
Michel L. Tremblay
Professor, Director of the McGill Cancer Centre
Role and function of protein tyrosine phosphatases
McGill Cancer Centre
Research Interests
Protein Tyrosine Phosphatases (PTPases) have been implicated in a variety of cellular processes such as cell growth, differentiation, and cancer. The nature of these enzymes suggests that they may be involved in cancer by acting either as anti-oncogenes or as oncogenes themselves. There is also evidence to suggest that PTPases are involved in mammalian development.
Our research interest has focused on three recently cloned enzymes and their relationship to mouse development and cancer. One of these PTPases, termed MPTP, is a ubiquitously expressed PTPase which localizes to the cell nucleus and may play a role in cell cycle events. MPTP-PEST is a ubiquitously expressed cytosolic enzyme which has been implicated in intracellular signal transduction. PTP NU-3 is a neuronal-cell specific PTPase which belongs to the receptor-type family of enzymes and is thought to play a role in neurogenesis by interacting with the extracellular matrix.
Our lab employs a variety of tools in the analysis of these PTPases. These include: cloning and identification of tissue specific and developmentally regulated PTPases; identification of in vivo substrates, associated proteins, and extracellular ligands; creation of temperature sensitive enzymes and cell lines; and the analysis of the gene expression pattern during mouse development. Together with transgenic and "knockout" mouse technology, these tools allow us to asses the role of these genes during mouse development as well as cellular events involved in cancer.
Publications - Michel Tremblay
相关基因：
PTPN1
Official Symbol: PTPN1 and Name: protein tyrosine phosphatase, non-receptor type 1 [Homo sapiens]
Other Aliases: PTP1B
Other Designations: non-receptor tyrosine phosphatase 1; protein tyrosine phosphatase 1B; protein tyrosine phosphatase, placental
Chromosome: 20; Location: 20q13.1-q13.2
MIM: 176885
GeneID: 5770
