Nonredundant functions for tumor protein D52-like proteins support specific targeting of TPD52.
OBJECTIVE
Tumor protein D52 (TPD52 or D52) is frequently overexpressed in breast and other cancers and present at increased gene copy number. It is, however, unclear whether D52 amplification and overexpression target specific functional properties of the encoded protein.


METHODS
The expression of D52-like genes and MAL2 was compared in breast tissues using quantitative reverse transcription-PCR. The functions of human D52 and D53 genes were then compared by stable expression in BALB/c 3T3 fibroblasts and transient gene knockdown in breast carcinoma cell lines. In situ D52 and MAL2 protein expression was analyzed in breast tissue samples using tissue microarray sections.


RESULTS
The D52 (8q21.13), D54 (20q13.33), and MAL2 (8q24.12) genes were significantly overexpressed in breast cancer tissue (n = 95) relative to normal breast (n = 7; P </= 0.005) unlike the D53 gene (6q22.31; P = 0.884). Subsequently, D52-expressing but not D53-expressing 3T3 cell lines showed increased proliferation and anchorage-independent growth capacity, and reduced D52 but not D53 expression in SK-BR-3 cells significantly increased apoptosis. High D52 but not MAL2 expression was significantly associated with reduced overall survival in breast carcinoma patients (log-rank test, P < 0.001; n = 357) and was an independent predictor of survival (hazard ratio, 2.274; 95% confidence interval, 1.228-4.210; P = 0.009; n = 328).


CONCLUSIONS
D52 overexpression in cancer reflects specific targeting and may contribute to a more proliferative, aggressive tumor phenotype in breast cancer.
Shehata
Mona
M
Molecular Oncology Laboratory, Oncology Research Unit, The University of Sydney Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead, Westmead 2145, New Zealand.
Bièche
Ivan
I
Boutros
Rose
R
Weidenhofer
Judith
J
Fanayan
Susan
S
Spalding
Lisa
L
Zeps
Nikolajs
N
Byth
Karen
K
Bright
Robert K
RK
Lidereau
Rosette
R
Byrne
Jennifer A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051379:Mice; D008875:Middle Aged; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000378:metabolism
C438606:MAL2 protein, human; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009363:Neoplasm Proteins; D011510:Proteolipids; C114751:TPD52 protein, human; C486416:TPD52L1 protein, human; D033921:Vesicular Transport Proteins