Murine cell lines derived from Pten null prostate cancer show the critical role of PTEN in hormone refractory prostate cancer development Journal Article
| Authors: | Jiao, J.; Wang, S.; Qiao, R.; Vivanco, I.; Watson, P. A.; Sawyers, C. L.; Wu, H. |
| Article Title: | Murine cell lines derived from Pten null prostate cancer show the critical role of PTEN in hormone refractory prostate cancer development |
| Abstract: | PTEN mutations are among the most frequent genetic alterations found in human prostate cancers. Our previous works suggest that although precancerous lesions were found in Pten heterozygous mice, cancer progression and metastasis only happened when both alleles of Pten were deleted. To understand the molecular mechanisms underlying the role of PTEN in prostate cancer control, we generated two pairs of isogenic, androgen receptor (AR)-positive prostate epithelial lines from intact conditional Pten knock-out mice that are either heterozygous (PTEN-P2 and -P8) or homozygous (PTEN-CaP2 and PTEN-CaP8) for Pten deletion. Further characterization of these cells showed that loss of the second allele of Pten leads to increased anchorage-independent growth in vitro and tumorigenesis in vivo without obvious structural or numerical chromosome changes based on SKY karyotyping analysis. Despite no prior exposure to hormone ablation therapy, Pten null cells are tumorigenic in both male and female severe combined immunodeficiency mice. Furthermore, knocking down PTEN can convert the androgen-dependent Myc-CaP cell into androgen independence, suggesting that PTEN intrinsically controls androgen responsiveness, a critical step in the development of hormone refractory prostate cancer. Importantly, knocking down AR by shRNA in Pten null cells reverses androgen-independent growth in vitro and partially inhibited tumorigenesis in vivo, indicating that PTEN-controlled prostate tumorigenesis is AR dependent. These cell lines will serve as useful tools for understanding signaling pathways controlled by PTEN and elucidating the molecular mechanisms involved in hormone refractory prostate cancer formation. ©2007 American Association for Cancer Research. |
| Keywords: | controlled study; gene deletion; mutation; cancer growth; nonhuman; cell proliferation; animal cell; mouse; animals; mice; mice, knockout; animal tissue; animal experiment; animal model; alleles; in vitro study; cell line, tumor; carcinogenesis; prostate cancer; prostatic neoplasms; homozygosity; gene expression regulation, neoplastic; heterozygosity; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; pten phosphohydrolase; prostate epithelium; androgen receptor; hormonal therapy; bicalutamide; karyotype; karyotyping; combined immunodeficiency; short hairpin rna; chromosomes; knockout mouse; structural chromosome aberration; numerical chromosome aberration; agar |
| Journal Title: | Cancer Research |
| Volume: | 67 |
| Issue: | 13 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-07-01 |
| Start Page: | 6083 |
| End Page: | 6091 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-06-4202 |
| PUBMED: | 17616663 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 32" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work