Evaluating the role of MEN1 gene expression and its clinical significance in breast cancer patients.

BACKGROUND: Breast cancer is a multifactorial disease which involves number of molecular factors that are critically involved in proliferation of breast cancer cells. MEN1 gene that is traditionally known for its germline mutations in neuroendocrine tumors is associated with high risk of developing breast cancer in females with MEN1 syndrome. However, the paradoxical role of MEN1 is reported in sporadic breast cancer cases. The previous studies indicate the functional significance of MEN1 in regulating breast cells proliferation but its relevance in development and progression of breast cancer is still not known. Our study targets to find the role of MEN1 gene aberration and its clinical significance in breast cancer. METHODS: Breast tumor and adjacent normal tissue of 142 sporadic breast cancer patients were collected at the time of surgery. The expression analysis of MEN1 mRNA and protein was done through RT-PCR, immunohistochemistry and western blotting. Further to find the genetic and epigenetic alterations, automated sequencing and MS-PCR was performed respectively. Correlation between our findings and clinical parameters was determined using appropriate statistical tests. RESULTS: MEN1 expression was found to be significantly increased in the breast tumor tissue with its predominant nuclear localization. The elevated expression of MEN1 mRNA (63.38% cases) and protein (60.56% cases) exhibited a significant association with ER status of the patients. Most of the cases had unmethylated (53.52%) MEN1 promoter region, which can be a key factor responsible for dysregulated expression of MEN1 in breast cancer cases. Our findings also revealed the significant association of MEN1 mRNA overexpression with Age and lymph node status of the patients. CONCLUSION: Our results indicate upregulated expression of MEN1 in sporadic breast cancer patients and it could be critically associated with development and advancement of the disease.

Mutation, methylation and expression analysis of LIFR gene in Indian breast cancer patients.

LIFR functions as a tumor suppressor and metastatic suppressor of breast cancer. The present study investigates the status of LIFR gene in Indian breast cancer patients. A total of 137 breast cancer tissue and 137 adjacent normal tissue which served as controls were analyzed for mutation by automated DNA sequencing, methylation through methylation-specific polymerase chain reaction and its corresponding expression at mRNA and protein level using real-time quantitative polymerase chain reaction and immunohistochemistry respectively in Indian breast cancer patients. All the molecular findings were statistically correlated with clinopathological parameters of the patients to identify its association. LIFR mRNA expression was found to be 2.534 ±â€¯3.52 fold downregulated with subsequent absence of protein in 67.15% cases (92/137). The absence of LIFR protein coincided with 80.95% (85/105) methylated cases thereby showing a very strong correlation among the LIFR promoter methylation and LIFR protein expression (p = 0.0001). We also observed G2968C nucleotide change in 6/137 cases of exon 20 of LIFR gene resulting in Glu990Gln mutation. Correlation of LIFR promoter methylation with geographic location and age at menopause and LIFR mutation with age at menarche, age at first live birth, molecular subtypes of breast cancer, and lymph node status remained significant even after bonferroni correction (p ≤ 0.0027). All these data suggests the relevance of these associations in relation to Indian breast cancer patients. The loss of LIFR protein was frequently found in Indian breast cancer patients, and aberrant promoter methylation showed a significant correlation with its downregulation.