Increased expression of annexin I is associated with drug-resistance in nasopharyngeal carcinoma and other solid tumors.

Adjuvant chemotherapy alongside radiotherapy is one of the effective therapies in nasopharyngeal carcinoma (NPC) treatment. However, the appearance of drug resistance is a major obstacle for anti-cancer chemotherapy and often causes failure of the chemotherapy. In this study, a drug-resistant gene annexin I (ANX-I) was identified by comparing differentially expressed proteins between a cisplatin (CDDP)-resistant NPC cell line CNE2-CDDP and parental CNE2 cells using 2-DE. When ANX-I was transfected into CNE2 cells, the CDDP resistance of CNE2 cells was dramatically increased. The drug-resistant ability of ANX-I was demonstrated by both in vitro and in vivo assays. The association of ANX-I expression with clinical features was also investigated. Increased expression of ANX-I was significantly associated with disease relapse in NPC (p<0.05). In breast and gastric cancer, increased expression of ANX-I was significantly associated with drug resistance (p<0.001) and poor prognosis (p<0.001), respectively. Taken together, our findings suggest that ANX-I plays an important role in drug resistance.

Isolation and characterization of a novel oncogene, amplified in liver cancer 1, within a commonly amplified region at 1q21 in hepatocellular carcinoma.

UNLABELLED: Amplification of 1q21 is the most frequent genetic alteration in human hepatocellular carcinoma (HCC), being detected in 58%-78% of primary HCC cases by comparative genomic hybridization. Recently, we isolated a candidate oncogene, Amplified in Liver Cancer 1 (ALC1), from 1q21 by hybrid selection. Here we demonstrate that ALC1 was frequently amplified and overexpressed in HCC. ALC1-transfected cells possessed a strong oncogenic ability, increasing the colony formation in soft agar and increasing the tumorigenicity in nude mice, which could be effectively suppressed by small interfering RNA against ALC1. Functional studies showed that overexpression of ALC1 could promote G1/S phase transition and inhibit apoptosis. Molecular studies revealed that the oncogenic function of ALC1 might be associated with its roles in promoting cell proliferation by down-regulating p53 expression. CONCLUSION: These results suggest that ALC1 is the target oncogene within the 1q21 amplicon and plays a pivotal role in HCC pathogenesis.

Oncogenic role of eIF-5A2 in the development of ovarian cancer.

Amplification of 3q26 is one of the most frequent chromosomal alterations in many solid tumors, including ovarian, lung, esophageal, prostate, breast, and nasopharyngeal cancers. A candidate oncogene to eukaryotic initiation factor 5A2 (eIF-5A2), a member of eukaryotic initiation factor 5A subfamily, has been isolated from a frequently amplified region at 3q26.2. In this work, the tumorigenic ability of eIF-5A2 was demonstrated by anchorage-independent growth in soft agar and tumor formation in nude mice. Furthermore, antisense DNA against eIF-5A2 could inhibit cell growth in ovarian cancer cell line UACC-1598 with amplification of eIF-5A2 in form of double minutes. Cell growth rate in UACC-1598 was also inhibited when the expression level of EIF-5A2 was decreased by the reduction of the copy number of double minutes. The correlation of EIF-5A2 overexpression and clinical features of ovarian cancer was investigated using tissue microarray, and the result showed that eIF-5A2 overexpression was significantly associated with the advanced stage of ovarian cancer. These findings suggest that eIF-5A2 plays important roles in ovarian pathogenesis.

Characterization of a complex chromosome rearrangement involving 6q in a melanoma cell line by chromosome microdissection.

Deletion of 6q is one of the most frequent chromosomal alterations in human malignant melanoma. Recently, we used chromosome painting probes of 6p and 6q to study 21 melanoma cell lines. A reciprocal translocation between chromosomes 6q and 17p was detected in one cell line (UACC-930). Upon further characterization of the translocation marker using the micro fluorescence in situ hybridization (FISH) technique, a complex rearrangement including an inversion of 6q and a translocation between the inverted 6q and 17p, [der(6)inv(6)(q16q27)t(6;17)(q26;p13)], was detected. A yeast artificial chromosome (YAC) clone spanning the breakpoint at 6q16 was isolated by the FISH screen. Loss of one or more copies of the YAC clone was also detected in 10 of 12 melanoma cell lines. This result implies that the YAC clone may contain a putative tumor suppressor gene related to the pathogenesis of malignant melanoma. Further characterizations of the breakpoint at 6q16 and molecular cloning breakpoints at 6q27 and 17p13 are in progress.