GDF3 inhibits the growth of breast cancer cells and promotes the apoptosis induced by Taxol.

PURPOSE: The aim of this study is to investigate whether GDF3 is related to the progression of human breast cancer and the effects of GDF3 on breast cancer cells. METHODS: The expression of GDF3 in 24 breast cancer specimens paired with corresponding neighboring nontumorous tissue was studied by Western blot. Breast cancer cells were treated with different concentrations of recombinant human GDF3 protein. Using lentivirus containing sh-RNA, we knocked down the expression of GDF3. Soft agar assay was performed to explore the effects of GDF3 on colony formation. Different anti-tumor drugs dealt with MCF-7 cells stably expressing GDF3. RESULTS: We found that GDF3 expression level was significantly down-regulated in breast cancer tissues compared to the surrounding nontumorous tissues. GDF3 proteins could inhibit the proliferation of MCF-7 and T47D cells. We also found that the knockdown of GDF3 resulted in the promotion of colony formation and enhanced the ability of anchorage-independent cell growth in soft agar. Furthermore, overexpression of GDF3 could promote the apoptosis induced by Taxol. CONCLUSIONS: Our data indicated that GDF3 expression is significantly decreased in human breast cancer tissues, and reconstitution of GDF3 in breast cancer may be a potential therapeutic approach to inhibit aggressive growth of breast cancer.

Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas.

Stem cell markers, OCT3/4, and more recently SOX2 and growth differentiation factor 3 (GDF3), have been reported to be expressed variably in germ cell tumors. We investigated the immunohistochemical expression of these markers in different testicular germ cell tumors, and their utility in the differential diagnosis of morphologically difficult-to-classify components of these tumors. A total of 50 mixed testicular germ cell tumors, 43 also containing difficult-to-classify areas, were studied. In these areas, multiple morphological parameters were noted, and high-grade nuclear details similar to typical embryonal carcinoma were considered 'embryonal carcinoma-like high-grade'. Immunohistochemical staining for OCT3/4, c-kit, CD30, SOX2, and GDF3 was performed and graded in each component as 0, negative; 1+, 1-25%; 2+, 26-50%; and 3+, >50% positive staining cells. The different components identified in these tumors were seminoma (8), embryonal carcinoma (50), yolk sac tumor (40), teratoma (40), choriocarcinoma (3) and intra-tubular germ cell neoplasia, unclassified (35). By immunohistochemistry, the staining patterns were OCT3/4 -3+, all seminomas, embryonal carcinomas and intra-tubular germ cell neoplasia; SOX2 -3+, all embryonal carcinomas and -2 to 3+, 11/14 (79%) primitive neuroectodermal components in immature teratomas; GDF3 -2 to 3+, all yolk sac tumors, seminomas and intra-tubular germ cell neoplasia and 1 to 2+, 40/50 embryonal carcinomas. A total of 34/43 (79%) of difficult-to-classify areas stained 3+ for OCT3/4, CD30, and SOX2, similar to embryonal carcinoma. Among these areas, only 'embryonal carcinoma-like high-grade' nuclear details were significantly associated with such an immunophenotype. Thus, SOX2 is expressed in embryonal carcinoma and primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ cell neoplasia and seminoma. Therefore, it may be useful in the distinction of seminoma from embryonal carcinoma, and potentially in diagnosing early carcinomatous differentiation in seminoma. GDF3 positivity, in the absence of OCT3/4 and CD30, combined with morphological features, is helpful in the diagnosis of yolk sac tumor. 'Embryonal carcinoma-like high-grade' nuclear details are the most important morphological criterion for the diagnosis of embryonal carcinoma in difficult-to-classify areas.