Copy number variability and dysregulation of specific pathways including androgen receptor signaling, PTEN/PAKT and TGF-β continue to play an important role in invasion and metastasis.
EGFR, pMAPK, pAkt and PTEN status by IHC were not significantly associated with response to trastuzumab, TTP, overall survival (OS1, OS2, OS3) and CNS metastases incidence.
Ex vivo introduction of MMAC/PTEN expression did not inhibit the tumorigenicity of orthotopically implanted PC3 cells, but it did significantly reduce tumor size and completely inhibited the formation of metastases.
Except for true de novo mutations in 4 cases (affecting SYNE1, CTNNB1, TP53, and PTEN), all remaining cases (84.4%) shared the genetic lesions of the primary tumors with all investigated metastases irrespective of the site of metastasis or time lapse between primary tumor resection and the occurrence of metastatic spread.
Finally, we identified that BMI-1 expression activating PI3K/AKT singing pathway by negative regulating PTEN was the main mechanism of promoting invasion and metastasis ability of pancreatic CSCs.
Five of 32 (16%) primary prostate cancers from Chinese men and two of six metastases from American men showed mutations in a total of 10 codons of PTEN, which involved exons 1, 2, 5, 8, and 9.
Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA.
Frozen tissue from primary cutaneous melanomas (n = 23) and metastases (n = 17) were microdissected, and microsatellite markers D10S541 and D10S547, flanking the gene on both sides, were used to search for loss of heterozygosity (LOH) in the PTEN gene locus.
Further, immunohistochemistry revealed significant correlation of decreased PTEN protein expression with PTEN genomic deletion both in localized and metastatic cancer.
Furthermore, PTEN loss in metastases may be predictive of resistance to anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical application.
Furthermore, apart from sporadic endometrial carcinoma, PTEN alteration in noncultured sporadic neoplasias likely occurs "late," promoting progression and metastasis.The article by Davies et al.
Furthermore, gain- and loss-of-function studies of the phosphatase and tensin homolog (PTEN) were performed to assess whether the effect of miR-92a promoted growth and metastasis of NSCLC cells were via targeting PTEN.
Furthermore, MAb159 halted or reversed tumor progression in the spontaneous PTEN-loss-driven prostate and leukemia tumor models, and inhibited tumor growth and metastasis in xenograft models.
Green fluorescent protein labeled TENN, a highly metastatic human colon cancer cell line with mutational loss of PTEN gene and TENN clones (with restoration of PTEN gene) tumors were orthotopically implanted onto the colons of BALB/c nude mice and allowed to develop primary and metastatic tumors.