Abstract:
:Invasive breast cancer has a high risk of recurrence to incurable disease and needs improved prognostic and therapeutic tools. Our work combines clinical and molecular analyses to show that the transcriptional repressor HBP1 may be a new target for invasive breast cancer. Previous work indicated that HBP1 regulated proliferation and senescence and inhibited Wnt signaling. Two of these functions have been associated with invasive breast cancer. In 76 breast tumors, we identified 10 HBP1 mutations/variants that were associated with fully invasive breast cancer. In a separate analysis, we found that a subset of invasive breast cancer specimens also had reduced HBP1 mRNA levels. These clinical correlations suggested that mutation or reduction of HBP1 occurs in invasive breast cancer and that HBP1 might regulate the proliferation and invasiveness of this breast cancer type. Analysis of the HBP1 mutants showed they were functionally defective for suppressing Wnt signaling. To test the consequences of reduced HBP1 levels, we used RNA interference to knock down HBP1 and observed increased Wnt signaling, tumorigenic proliferation, and invasiveness in cell and animal breast cancer models. Lastly, statistical analysis of a breast cancer patient database linked reduced HBP1 expression to breast cancer recurrence. In considering two-gene criteria for relapse potential, reduced expression of HBP1 and SFRP1, which is another Wnt inhibitor that was recently linked to invasive breast cancer, strikingly correlated with recurrence. Together, these data indicate that HBP1 may be a molecularly and clinically relevant regulator of breast cancer transitions that eventually lead to poor prognosis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Paulson KE,Rieger-Christ K,McDevitt MA,Kuperwasser C,Kim J,Unanue VE,Zhang X,Hu M,Ruthazer R,Berasi SP,Huang CY,Giri D,Kaufman S,Dugan JM,Blum J,Netto G,Wazer DE,Summerhayes IC,Yee ASdoi
10.1158/0008-5472.CAN-07-0567subject
Has Abstractpub_date
2007-07-01 00:00:00pages
6136-45issue
13eissn
0008-5472issn
1538-7445pii
67/13/6136journal_volume
67pub_type
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