5915

RARB

retinoic acid receptor, beta;RARB;retinoic acid receptor, beta

HBV-activated protein|RAR-beta|RAR-epsilon|hepatitis B virus activated protein|nuclear receptor subfamily 1 group B member 2|retinoic acid receptor beta|retinoic acid receptor, beta polypeptide

3p24.2

protein-coding

The human retinoic acid receptor beta (RARbeta) has three isoforms (beta1, beta2, and beta4), which play important, distinct roles in mediating the effects of retinoic acid on cell growth and apoptosis. Whereas RARbeta2 is a potent inhibitor of breast cancer cell proliferation, RARbeta4 can act as a dominant-negative repressor of RARbeta2-mediated growth suppression. In this study we investigated the effects of all-trans-retinoic acid (ATRA) on two clones derived from the breast cancer cell line MDA-MB-435: a non-metastatic clone (NM-2C5) and a metastatic clone (M-4A4). ATRA treatment of the NM-2C5 cells resulted in growth inhibition and apoptosis, whereas the M-4A4 cells were resistant to ATRA. Analyses of the expression of RARbeta isoforms revealed that the sensitive NM-2C5 clone expressed only RARbeta2, whereas the resistant M-4A4 cells expressed both RARbeta2 and RARbeta4 mRNA and protein. ATRA treatment increased RARbeta2 mRNA level in NM-2C5 cells, whereas the same treatment of the M-4A4 cells resulted in an increase in RARbeta4 and a decrease in RARbeta2 mRNA. ATRA treatment of NM-2C5 cells increased the protein levels of the histone acetyl transferases p300 and CBP, suppressed the level of histone deacetylase and increased the level of acetylated histone H4. ATRA also decreased Bcl-2 and increased Bax and decreased VEGF. In contrast, the same treatment of the M-4A4 cells resulted in opposite effects. These results suggest that the effects of ATRA on the growth of the metastatic and non-metastatic breast cancer cell lines depend on the expression of RARbeta isoforms and that the expression of RARbeta4 may contribute to metastatic properties.

OBJECTIVE: To investigate the expression and its significance of retinoic acid receptor-beta (RAR-beta) in colorectal cancer. METHODS: RAR-beta was detected by immunohistochemistry methods and carcino-embryonic antigen (CEA) was tested by chemiluminescence immunoassay methods in normal tissues, paracancerous tissues and colorectal cancer tissues of 60 patients with colorectal cancer treated from January 2006 to January 2007. Above-mentioned data, together with the clinicopathological data of these 60 patients, were analyzed to figure out the expression and its significance of RAR-beta in colorectal cancer. RESULTS: The expression rate of RAR-beta in tumor tissues (48%) was significantly lower than those in both normal tissues (87%) and paracancerous tissues (87%) (P < 0.05). And its expression was also significant lower in patients with lymph node metastasis (32%) and patients with advanced cancer (TNM stage III and IV) (29%) than in those without lymph nodes metastasis (60%) and those with early stage cancer (stage I and II) (69%). There was no significant differences among well, mildly and poorly differentiated cancer tissues. The CEA level rose in 20 patients, and its rising rate was remarkably higher in patients with lymph node metastasis (48%) and in patients with advanced cancer (52%) than those without lymph node metastasis (23%) and in early stage(14%). CONCLUSIONS: The expression of RAR-beta decreases significantly in cancer tissues in patients with colorectal cancer, which may be related to the carcinogenesis of colorectal cancer; and its decreasing degree is correlated negatively with the lymph node metastasis and advanced clinicopathological stage. The expression level of RAR-beta may be a new prognostic indication of patients with colorectal cancer.

OBJECTIVE: To study the methylation status of retinoic acid receptor beta2 (RARbeta2) and p16(INK4alpha) genes in peripheral blood and tumor tissues and the perioperative dynamic changes of free RARbeta2 and p16(INK4alpha) in the peripheral blood, and to investigate the relationship between RARbeta2 and p16(INK4alpha) methylation in peripheral blood and clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) and their value in evaluating the completeness of surgical resection. METHODS: Real-time methylation specific polymerase chain reaction (real-time MSP) technique was used to detect the methylation status of RARbeta2 and p16(INK4alpha) in tumor tissue, adjacent normal tissue and peripheral blood perioperatively in 76 cases of ESCC. Sixty age-matched healthy volunteers were randomly selected as a control. RESULTS: RARbeta2 and p16(INK4alpha) hypermethylation presented in both tumor tissue [72.4% (55/76) and 86.8% (66/76)] and peripheral blood [63.2% (48/76) and 71.1% (54/76)] in the ESCC patients, showing a good agreement between them. RARbeta2 and p16(INK4alpha) hypermethylation was significantly related with pathological stage, lymph node metastasis, and invasion of nerves and vessels (P < 0.05). The DNA methylation rate in peripheral blood was increasing first and then decreasing in the preoperative, intraoperative and postoperative periods. Moreover, the RARbeta2 methylation in peripheral blood was shown to be significantly associated with family history of cancer (P = 0.023). CONCLUSION: RARbeta2 and p16(INK4alpha) methylation in the peripheral blood in ESCC patients may reflect the tumor-bearing status in the body, and may serve as a valuable marker in assessment of the degree of completeness of surgical resection in ESCC patients.