PTEN and NEDD4 in Human Breast Carcinoma.
PTEN is an important tumor suppressor gene that antagonizes the oncogenic PI3K/AKT signaling pathway and has functions in the nucleus for maintaining genome integrity. Although PTEN inactivation by mutation is infrequent in breast cancer, transcript and protein levels are deficient in >25 % of cases. The E3 ubiquitin ligase NEDD4 (also known as NEDD4-1) has been reported to negatively regulate PTEN protein levels through poly-ubiquitination and proteolysis in carcinomas of the prostate, lung, and bladder, but its effect on PTEN in the breast has not been studied extensively. To investigate whether NEDD4 contributes to low PTEN levels in human breast cancer, we analyzed the expression of these proteins by immunohistochemistry across a large Swedish cohort of breast tumor specimens, and their transcript expression levels by microarrays. For both NEDD4 and PTEN, their transcript expression was significantly correlated to their protein expression. However, comparing NEDD4 expression to PTEN expression, either no association or a positive correlation was observed at the protein and transcript levels. This unexpected observation was further corroborated in two independent breast cancer cohorts from The Netherlands Cancer Institute and The Cancer Genome Atlas. Our results suggest that NEDD4 is not responsible for the frequent down-regulation of the PTEN protein in human breast carcinoma.
Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.|Lund University Cancer Center, Lund, Sweden.
Yilun
Y
Chen
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Marc J
MJ
van de Vijver
Department of Pathology, Columbia University Medical Center, NY, USA.
Hanina
H
Hibshoosh
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, NY, USA.
Ramon
R
Parsons
Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden. lao.saal@med.lu.se.|Lund University Cancer Center, Lund, Sweden. lao.saal@med.lu.se.|CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund, Sweden. lao.saal@med.lu.se.
Lao H
http://orcid.org/0000-0002-0815-1896
LH
Saal
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D000075702:Nedd4 Ubiquitin Protein Ligases; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D056827:Endosomal Sorting Complexes Required for Transport; D012333:RNA, Messenger; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Breast carcinoma; IHC; NEDD4; PTEN