The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance.

Abstract:

:Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The non-malignant form of the disease is termed chondroma. Correctly distinguishing between the two forms is essential for making therapeutic decisions. However, due to their similar histological appearances and the lack of a reliable diagnostic marker, it is often difficult to distinguish benign tumors from low-grade chondrosarcoma. Therefore, it is necessary to search for a potential marker that has diagnostic and prognostic values in chondrosarcoma. In this study, we demonstrated by immunohistochemistry that elevated leukemia/lymphoma-related factor (LRF) expression was associated with increased malignancy in human chondrosarcoma tissue microarrays. Moreover, siRNA depletion of LRF drastically reduced proliferation of chondrosarcoma cell lines and effectively induced senescence in these cells. This could be attributed to the observation that LRF-depleted cells were arrested at the G(1) phase, and had increased p53 and p21 expression. Moreover, LRF depletion not only drastically reduces the cellular migration and invasion potentials of chondrosarcoma cells but also sensitized these cells to the apoptosis-inducing chemotherapeutic agent doxorubicin. We conclude that LRF is a survival factor in chondrosarcomas and its expression correlates with tumor malignancy and chemoresistance. Our data implicate the potential role of LRF as both a diagnostic marker and therapeutic target for chondrosarcomas.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Kumari R,Li H,Haudenschild DR,Fierro F,Carlson CS,Overn P,Gupta L,Gupta K,Nolta J,Yik JH,Di Cesare PE

doi

10.1093/carcin/bgs254

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

2076-83

issue

11

eissn

0143-3334

issn

1460-2180

pii

bgs254

journal_volume

33

pub_type

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