Loss of transformed phenotype in cancer cells by overexpression of the uteroglobin gene

Citation
Zj. Zhang et al., Loss of transformed phenotype in cancer cells by overexpression of the uteroglobin gene, P NAS US, 96(7), 1999, pp. 3963-3968
Citations number
36
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
96
Issue
7
Year of publication
1999
Pages
3963 - 3968
Database
ISI
SICI code
0027-8424(19990330)96:7<3963:LOTPIC>2.0.ZU;2-P
Abstract
Uteroglobin (UG) is a multifunctional, secreted protein that has receptor-m ediated functions. The human UG (hUG) gene is mapped to chromosome 11q12.2- 13.1, a region frequently rearranged or deleted in many cancers. Although h igh levels of hUG expression are characteristic of the mucosal epithelia of many organs, hUG expression is either drastically reduced or totally absen t in adenocarcinomas and in viral-transformed epithelial cells derived from the same organs. In agreement with these findings, in an ongoing study to evaluate the effects of aging on UG-knockout mice, 16/16 animals developed malignant tumors, whereas the wild-type littermates (n = 25) remained appar ently healthy even after 1 1/2 years. In the present investigation, we soug ht to determine the effects of induced-expression of hUG in human cancer ce lls by transfecting several cell lines derived from adenocarcinomas of vari ous organs with an hUG-cDNA construct. We demonstrate that induced hUG expr ession reverses at least two of the most important characteristics of the t ransformed phenotype (i.e., anchorage-independent growth on soft agar and e xtracellular matrix invasion) of only those cancer cells that also express the hUG receptor. Similarly, treatment of the nontransfected, receptor-posi tive adenocarcinoma cells with purified recombinant hUG yielded identical r esults. Taken together, these data define receptor-mediated, autocrine and paracrine pathways through which hUG reverses the transformed phenotype of cancer cells and consequently, may have tumor suppressor-like effects.