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Hidefumi Sasaki

Publications and source records attributed to Hidefumi Sasaki.

At least 19 recordsLinked to original sources
PubMed2007

EGFRvIII mutation in lung cancer correlates with increased EGFR copy number.

Overexpression of the epidermal growth factor receptor (EGFR) is caused by EGFR gene amplification and is sometimes associated with expression of a variant EGFR (deletion exon 2-7 or EGFRvIII). EGFRvIII mutation has oncogenic potential and is investigated as a potential therapeutic target. We genotyped the EGFRvIII mutation status in 252 surgically treated lung cancer cases. The presence or absence of EGFRvIII mutation was analyzed by real-time quantitative polymerase chain reaction (PCR) with mutation specific sensor and anchor probes. EGFR copy number was evaluated with PCR-based assay. EGFR mutation status at kinase domain has been examined and reported. EGFRvIII mutation was found on 8 of 252 patients. All patients were male, smokers, and 7 had squamous cell carcinoma. The mutation status was significantly correlated with pathological subtypes (squamous cell carcinoma vs. adenocarcinoma, p=0.0114). Sixty EGFR mutations at kinase domain exclusively existed with EGFRvIII mutations. EGFR gene copy number was significantly higher in EGFRvIII mutant (4.711+/-4.968) than in non-EGFRvIII mutant (2.284+/-1.224) (p=0.0001). EGFRvIII gene mutation might be one of the mechanisms of increased EGFR copy number. Further studies are needed to confirm the mechanisms of EGFRvIII mutations for possible anti-EGFR therapy for lung cancer.

Adenocarcinoma↗
PubMed2006

Mutation of epidermal growth factor receptor gene in adenosquamous carcinoma of the lung.

We have investigated 26 adenosquamous lung cancer tissues and found that four EGFR mutations were mainly in female and non-smoker lung cancer. However, EGFR mutation at kinase domain was exclusive with K-ras mutation. However, smoking and gender status could affect the occurrence of EGFR mutation. There was no difference in EGFR mutation status if analysis was performed in never smoker female subgroup.

Aged↗
PubMed2006

PIK3CA mutation status in Japanese lung cancer patients.

Somatic mutations of the PIK3CA (phosphatidylinostitol 3-kinase catalytic subunit) gene have been found in human cancer patients. Previous reports suggested that about 4% of lung cancers harbored PIK3CA gene mutations. However, the clinico-pathological background for PIK3CA gene mutations has not yet been investigated in lung cancer. We have genotyped the PIK3CA gene in Japanese lung cancer patients. The study included 235 lung cancer cases surgically removed in Nagoya City University Hospital. The two PIK3CA mutation hot spots (exon 9 and exon 20) were analyzed by real time polymerase chain reaction (PCR)-based assay. The data were confirmed by direct sequencing. In exon 9, somatic mutation was found in eight patients (3.4%). The mutation included three E542K (G1624A), three E545K (G1633A), one E542Q (G1624C), and one Q546K (C1636A). However, in exon 20, there was no mutation in our lung cancer patients. PIK3CA mutations were not correlated with gender (women versus men, p=0.4162), age (< or =60 versus >60, p=0.8027), or smoking status of the lung cancers (never versus smoker, p=0.5666). PIK3CA mutation incidence was significantly lower in adenocarcinoma (2/135, 1.5%) than in squamous cell carcinoma (5/77, 6.5%, p=0.0495). Among eight patients with a PIK3CA mutation, three patients also harbored an EGFR somatic mutation. PIK3CA gene mutations were rare in lung cancer; rarer in adenocarcinoma. Further functional analyses of the PIK3CA mutations are warranted to study if they could be the target of therapy for the lung cancer.

Adenocarcinoma↗
PubMed2006

L858R EGFR mutation status correlated with clinico-pathological features of Japanese lung cancer.

Somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in about 25-40% of Japanese lung cancer patients. These mutations are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors. Most common mutation are arginine for leucine substitution at amino acid 858 (L858R) and exon 19 deletions, especially deletion type 1 mutation. We investigated these EGFR mutation statuses in 575 surgically treated non-small cell lung cancer (NSCLC) cases. Three-hundred and sixty-two adenocarcinoma cases were included. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis (TaqMan assay; n=386, and LightCycler assay; n=98) and sequences (n=91). EGFR mutations (CTG; CGG; L858R) were found from 63 of 575 lung cancer patients. We also detected the deletion 1a type mutations (2235-2249 del GGAATTAAGAGAAGC) from 39 patients and deletion 1b type mutations (2236-2250 del GAATTAAGAGAAGCA) from 15 patients in exon 19. These mutation statuses were significantly correlated with gender, smoking status (never smoker versus smoker), and pathological subtypes (adenocarcinoma versus non-adenocarcinoma). L858R mutation (p<0.0001), but not deletion 1 type mutation (p=0.0665), was correlated with differentiation status (well versus moderately or poorly) of lung cancers. L858R mutation ratio was significantly higher in non-smoker (p=0.0496) and adenocaicinoma (p=0.0136) when compared to deletion 1 type mutations. The EGFR mutation status, especially L858R mutation might be correlated with the clinico-pathological features related to good response to gefitinib, such as gender, smoking history, and pathological subtypes of Japanese lung cancers.

Adenocarcinoma↗
PubMed2006

Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.

The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence variations by independent and parallel sampling of multiple representatives of a given DNA fragment. This technology can thereby facilitate accurate molecular diagnosis of heterogeneous cancer specimens and enable patient selection for targeted cancer therapies.

Base Sequence↗
PubMed2006

Expression and mutation statuses of epidermal growth factor receptor in thymic epithelial tumors.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations have been reported to correlate with the sensitivity to the tyrosine kinase inhibitor treatment for advanced lung cancers. Since several reports have shown that invasive thymoma overexpress the EGFR protein, we examined the EGFR expression and mutation statuses in thymoma and thymic carcinoma tissues. METHODS: EGFR mutation statuses from 99 thymic epithelial tumor samples were evaluated by a rapid and sensitive TaqMan assay using Applied Biosysytems 7500 real-time PCR system. Probes were designed according to the 13 different EGFR mutations reported previously in lung cancers. A total of 38 thymoma samples were directly sequenced for the EGFR gene. Protein expressions were evaluated for 56 thymic epithelial tumors by immunohistochemistry. RESULTS: EGFR gene mutations were not detected in any of the thymoma and thymic cancer samples using TaqMan PCR assay. Of the 38 samples 3 showed a heterozygous silent mutation without changes in the protein, a G to A transition at the nucleotide 2361 in exon 18. EGFR expression was significantly higher in invasive thymomas (stages III-IV, 15/19 were positive) than in early stage thymomas (stages I-II, 7/33 were positive) (P < 0.0001). All four carcinomas and all seven B3 thymomas showed EGFR positive staining. CONCLUSIONS: Although EGFR mutation at the tyrosine kinase domain is unlikely to be a therapeutic target for thymoma, the information about EGFR expression would contribute to the further identification of the therapeutic target for advanced thymomas.

Adult↗
PubMed2006

Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors.

The tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) have shown anti-tumor activity in the treatment of non-small cell lung cancer (NSCLC). Dramatic and durable responses have occurred in NSCLC tumors with mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). In contrast, these inhibitors have shown limited efficacy in glioblastoma, where a distinct EGFR mutation, the variant III (vIII) in-frame deletion of exons 2-7, is commonly found. In this study, we determined that EGFRvIII mutation was present in 5% (3/56) of analyzed human lung squamous cell carcinoma (SCC) but was not present in human lung adenocarcinoma (0/123). We analyzed the role of the EGFRvIII mutation in lung tumorigenesis and its response to tyrosine kinase inhibition. Tissue-specific expression of EGFRvIII in the murine lung led to the development of NSCLC. Most importantly, these lung tumors depend on EGFRvIII expression for maintenance. Treatment with an irreversible EGFR inhibitor, HKI-272, dramatically reduced the size of these EGFRvIII-driven murine tumors in 1 week. Similarly, Ba/F3 cells transformed with the EGFRvIII mutant were relatively resistant to gefitinib and erlotinib in vitro but proved sensitive to HKI-272. These findings suggest a therapeutic strategy for cancers harboring the EGFRvIII mutation.

Animals↗
PubMed2006

Preoperative steroid pulse therapy for invasive thymoma: clinical experience and mechanism of action.

BACKGROUND: Glucocorticoid was used in thymomas. The purpose of the study was to evaluate the efficacy of intravenous high-dose glucocorticoid (steroid pulse) therapy in patients with previously untreated advanced thymoma. Causes were also sought for a possible underlying mechanism of the effect of steroid on thymoma. METHODS: Seventeen patients with invasive thymoma who had not received previous chemotherapy or radiation therapy were enrolled in the study. All cases were treated with 2 courses of glucocorticoid therapy before surgery. Tumor response was assessed by computed tomography (CT) scan 1 week after the steroid pulse therapy. Lymphocytes associated with thymoma were analyzed for their CD4/CD8 phenotype and glucocorticoid receptor (GR). TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining was used to analyze the apoptotic lymphocytes and epithelial cells. RESULTS: The overall response rate to the steroid pulse therapy was 47.1% (8 of 17). The reduction in tumor size was most prominent in type B1 thymomas; there were significant differences between type AB and type B1 thymomas (P = .0234) and type B1 and type B3 thymomas (P = .0068). The reduction in tumor size was accompanied with a marked reduction in the CD4+8+ double-positive immature thymocytes that expressed higher levels of glucocorticoid receptor. Apoptotic changes were observed in both neoplastic epithelial cell and lymphocyte components after glucocorticoid therapy. CONCLUSIONS: The efficiency of preoperative steroid pulse therapy in type B1 thymoma was most prominent, which is probably related to the specific effect on GR-rich CD4+8+ double-positive immature lymphocytes, which are abundant in this type of thymoma.

Adult↗
PubMed2006

Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung.

Epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung cancer, especially in adenocarcinoma, in females, and non-smoking patients. EGFR mutations are closely associated with clinical response to EGFR tyrosine kinase inhibitor. Bronchioloalveolar carcinoma (BAC) appearance is a good predictor of response to this agent. Noguchi et al. subdivided small peripheral adenocarcinoma of the lung into two groups. One group was characterized with tumor cell growth replacing the normal alveolar cells with varying degree of fibrosis (types A-C), and the other shows non-replacing and destructive growth (types D-F). Using probes for the 13 mutations which have been previously described, we have genotyped the EGFR gene status in surgically resected atypical adenomatous hyperplasias (AAH) and small peripheral adenocarcinomas up to 2 cm in diameter using TaqMan PCR assay. In 95 small-sized adenocarcinomas, the EGFR mutations were detected in 37 patients (38.9%), and no mutations were found in five AAHs. In small peripheral adenocarcinomas, EGFR mutations were found 47.1% of types A, B, or C adenocarcinomas; it was less frequent (16%) in Noguchi's types D, E or F adenocarcinomas. These results suggest that type D, F adenocarcinomas are not derived from the less malignant types A-C adenocarcinomas; rather, they have arisen de novo by distinct mechanisms. Although types A and B adenocarcinomas are almost 100% cured by surgery, some type C adenocarcinoma show lymph node metastasis and relapse. EGFR mutation analysis may help identify patients who will respond to treatment with tyrosine kinase inhibitors, e.g., gefitinib.

Adenocarcinoma↗
PubMed2006

A correlation between EGFR gene mutation status and bronchioloalveolar carcinoma features in Japanese patients with adenocarcinoma.

BACKGROUND: The presence of epidermal growth factor receptor (EGFR) mutations in gefitinib-naive lung cancer patients has been reported to be higher in females, in non-smokers, in Japanese, and in adenocarcinoma patients, especially in bronchioloalveolar carcinoma (BAC). To further investigate the prevalence of EGFR mutations in relation to pathological factors, we evaluated EGFR mutations in series of Japanese adenocarcinoma patients who had never been treated with gefitinib. METHODS: In the previous studies, we examined mutation status in the tyrosine kinase domain of EGFR, exon18 through exon21, in 112 primary lung adenocarcinoma samples. Using these data, adenocarcinomas were histologically classified according to the presence or absence of bronchioloalveolar components. RESULTS: Among 112 patients, 48 had adenocarcinoma with BAC components. Those with adenocarcinomas with BAC components had higher frequency of EGFR mutation (28/48, 58%) than those with non-BAC adenocarcinoma (24/64, 37%, P = 0.036). Male patients had the same trend; 12/23 (52%) male patients with adenocarcinoma with BAC components and 10/47 (21%) of those with non-BAC adenocarcinoma had EGFR mutation (P = 0.0135) but there was no correlation between the EGFR mutation status and with/without BAC components in 42 female patients (P = 0.30). Among 11 male non-smokers, patients with adenocarcinoma with BAC components had a tendency to have EGFR mutation more frequently than those with non-BAC adenocarcinoma (P = 0.061). In clear contrast, the frequency of EGFR mutation did not differ significantly between male smoker patients with adenocarcinoma with BAC components and those with non-BAC. Among patients with adenocarcinoma with BAC components, those with adenocarcinoma with EGFR gene mutation had a significantly better 5 year survival than those with adenocarcinoma with wild-type (85.7 versus 46.0%, P = 0.0017). CONCLUSIONS: Adenocarcinomas with BAC components in male non-smokers seem to predict the presence of EGFR mutation. Half of female adenocarcinoma patients with EGFR mutation exhibit adenocarcinomas with non-BAC suggesting a different behavior from those in males. The prognosis of patients with adenocarcinoma with BAC components with EGFR gene mutation is predicted to be better than that of patients with adenocarcinoma with BAC components with wild-type EGFR gene.

Adenocarcinoma↗
PubMed2006

EGFR and erbB2 mutation status in Japanese lung cancer patients.

Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Somatic mutations of the EGFR gene were found in about 25-40% of Japanese lung cancer patients. More recently, erbB2 mutations are found in about 4% of European-derived lung cancer patients. We have investigated EGFR and erbB2 mutation status in 95 surgically treated nonsmall cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Seventy-five adenocarcinoma cases were included. The presence or absence of EGFR and ernB2 mutations of kinase domains were analyzed by reverse transcription polymerase chain reaction (RT-PCR) amplifications and direct sequences. We have also investigated erbB2 mutation status in 27 surgically treated NSCLC cases followed by treatment with gefitinib from Kinki-chuo Chest Medical Center. EGFR mutations (CTG-->CGG; L858R) were found from 14 of 95 lung cancer patients. We also detected the deletion 1a-type mutations from 9 patients and deletion 4-type mutations from 6 patients in exon 19. In exon 20, 4 mutations including 2 novel mutations were found. Total EGFR mutations were present in 35 patients (36.8%). These mutation statuses were significantly correlated with gender (women 73.3% vs. men 20%, p < 0.0001), smoking status (never smoker 69.4% vs. smoker 16.9%, p < 0.0001), pathologic subtypes (adenocarcinoma 45.1% vs. nonadenocarcinoma 12.5%, p = 0.0089) and differentiation status of the lung cancers (well 51% vs. moderately or poorly 18.4%, p = 0.0021). On the other hand, erbB2 mutation was only found from 1 of 95 patients, at exon 20. This patient was female and a never smoker with adenocarcinoma. This 12 nucleotide insertion mutation (2324-2325 ins ATACGTGATGGC) was located in the exon 20 at kinase domain (775-776 ins YVMA). There was no erbB2 mutation in 27 gefitinib-treated NSCLC patients. In total, we have found only 1 erbB2 mutation from 122 (0.8%) Japanese NSCLC patients. There was a significantly higher erbB2 positive (2+/3+) ratio in EGFR mutant patients (13/25, 52.0%) compared to EGFR wild-type patients (10/62, 16.1%; p = 0.0247). The NSCLC specimen with erbB2 mutation showed 1+ immunoreactivity. The EGFR mutation status might correlate with the clinicopathologic features related to good response to gefitinib, such as gender, smoking history and pathologic subtypes of lung cancers. However, erbB2 mutation is rare from Japanese lung cancer and is of limited value for molecular target therapy.

Aged↗
PubMed2006

Right partial anomalous pulmonary venous connection found during lobectomy for coexisting lung cancer and tuberculosis: report of a case.

Herein, we report a rare case of a 59-year-old man in whom a partial anomalous pulmonary venous connection was found during an operation for coexisting lung cancer and tuberculosis. It was observed that the anomalous vein drained only from the right upper lobe into the right superior vena cava. The middle and lower pulmonary veins connected normally, and there was no atrial septal defect or any other anomalous condition. An upper lobectomy for coexisting lung cancer and tuberculosis with ligation of the partial anomalous pulmonary venous connection was successfully performed.

Comorbidity↗
PubMed2006

Decreased fragile histidine triad gene messenger RNA expression in lung cancer.

BACKGROUND: The fragile histidine triad (FHIT) gene is located at 3p14.2, a region frequently lost in various tumor types. Lack of FHIT expression has been found to occur frequently in multiple tumor types including lung cancer. We have investigated FHIT messenger RNA (mRNA) levels and other clinicopathologic data, including FHIT and p21 expression in lung cancer. PATIENTS AND METHODS: The study included 97 lung cancer cases. The FHIT mRNA levels were quantified by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using LightCycler. RESULTS: The FHIT/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were decreased in tumor tissues from lung cancer (13.844 +/- 33.047) compared with adjacent nonmalignant lung tissues (195.763 +/- 678.469; P < 0.0001). No significant difference in FHIT/GAPDH mRNA levels was found among age, T status, or lymph node metastasis. The FHIT/GAPDH mRNA level was less in squamous cell carcinoma (0.144 +/- 0.246), a smoking-related cancer, than in adenocarcinoma (0.72 +/- 1.321; P = 0.0355). FHIT/GAPDH mRNA levels were correlated with FHIT protein (P = 0.0139) and p21 protein (P = 0.0484) expression by immunohistochemistry. The prognosis for patients with lung cancer with low FHIT/GAPDH levels (< 0.26; n = 57) was significantly worse than in the patients with high FHIT/GAPDH levels (> 0.26; n = 40; log-rank test, P = 0.0404). CONCLUSION: Using the LightCycler RT-PCR assay, decreased FHIT gene expression might occur early and play an important role in lung tumorigenesis and also correlate with the prognosis of lung cancer. However, further studies are needed to confirm the impact of FHIT in the biologic behavior of the tumor.

Acid Anhydride Hydrolases↗
PubMed2006

Decreased kallikrein 11 messenger RNA expression in lung cancer.

BACKGROUND: Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. A recently developed method for measuring hK11 suggested that the hK11 level was an indicator of favorable prognosis in patients with ovarian cancer. We have investigated hK11 messenger RNA (mRNA) levels in lung cancer. PATIENTS AND METHODS: This study included 64 lung cancer cases. The hK11 mRNA levels were quantified by real-time reverse-transcriptase polymerase chain reaction using LightCycler. RESULTS: The hK11 mRNA levels were lower in tumor tissues from lung cancer (1.88 +/- 6.314) compared with adjacent nonmalignant lung tissues (8.271 +/- 9.002; n = 45; P = 0.0001). No significant difference was found among sex, age, clinical stages, tumor status, and lymph node metastasis. The hK11 mRNA levels were lower in moderately or poorly differentiated adenocarcinoma lung cancer (0.452 +/- 1.614) compared with well-differentiated adenocarcinoma lung cancer (1.728 +/- 2.829; P = 0.0281). The group with low hK11/gylceraldehyde 3-phosphate dehydrogenase levels (< 0.6) had a significantly worse prognosis compared with the group with high hK11/gylceraldehyde 3-phosphate dehydrogenase levels (> 0.6; log-rank test, P = 0.0131; Breslow-Gehan-Wilcoxon test, P = 0.0172). CONCLUSION: Cox proportional hazard regression model (multivariate analysis) indicated that pathologic stages (P = 0.0443) and low hK11 expression levels (P = 0.0469) were the prognostic factors of lung cancers. However, additional studies and a longer follow-up are needed to confirm the impact of hK11 on the biologic behavior of the tumor.

Adenocarcinoma↗
PubMed2006

Evaluation of the epidermal growth factor receptor gene mutation and copy number in non-small cell lung cancer with gefitinib therapy.

Several studies have suggested that epidermal growth factor receptor (EGFR) gene mutation, EGFR gene amplification, and some other biomarkers may be predictors of gefitinib sensitivity. We analyzed EGFR mutation and EGFR copy number in 22 gefitinib-treated non-small cell lung cancer (NSCLC) cases and their relation to the survival of patients. We also studied 143 gefitinib-naïve Japanese NSCLC cases. The erbB2 copy number was also studied in 59 gefitinib-naïve NSCLC cases. In gefitinib-treated patients, the presence of EGFR mutation was associated with a higher response rate to gefitinib and a longer overall survival, but the increased EGFR gene copy number was not. In gefitinib-naïve cases, EGFR mutation but not EGFR gene copy number was significantly correlated with gender, pathological subtypes, and smoking status. The erbB2 copy number was not significantly correlated with the EGFR mutation or EGFR copy number in 59 cases. In conclusion, EGFR mutation was a better predictor of clinical outcome in gefitinib-treated patients than the EGFR gene copy number.

Adenocarcinoma↗
PubMed2005

Uncommon V599E BRAF mutations in Japanese patients with lung cancer.

BACKGROUND: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene and Braf gene were found in patients with lung cancer. These mutations might be correlated with a clinical response to molecular target therapy. Although a few Caucasian lung cancer patients harbored BRAF mutations, there have been no reports about the BRAF mutation in Japanese patients with lung cancer. MATERIALS AND METHODS: We investigated BRAF mutations in Japanese lung cancer patients. The study included 129 surgically removed lung cancer cases from Nagoya City University Hospital. Braf, EGFR, and erbB2 mutations also were analyzed by reverse transcript polymerase chain reaction (RT-PCR) and direct sequencing. RESULTS: In exon 15, one BRAF mutation (1796 thymine to adenine; V599E) was found in nonsmoking woman with well-differentiated adenocarcinoma. We detected the 43 EGFR mutations, including 19 at exon 19 and 20 at exon 21 from the 129 patients analyzed (33.3%). We also detected one erbB2 mutation from 76 patients analyzed. All these mutations existed exclusively. CONCLUSIONS: V599E BRAF mutation was uncommon in Japanese lung cancer. All three genes mutations were predominantly found in female nonsmoking subjects with adenocarcinomas. However, completely exclusive mutation status would help us to choose custom-made molecular target therapy for the lung cancer.

Adenocarcinoma↗
PubMed2005

HIN-1, an inhibitor of cell growth, invasion, and AKT activation.

The HIN-1 gene encoding a small, secreted protein is silenced due to methylation in a substantial fraction of breast, prostate, lung, and pancreatic carcinomas, suggesting a potential tumor suppressor function. The receptor of HIN-1 is unknown, but ligand-binding studies indicate the presence of high-affinity cell surface HIN-1 binding on epithelial cells. Here, we report that HIN-1 is a potent inhibitor of anchorage-dependent and anchorage-independent cell growth, cell migration, and invasion. Expression of HIN-1 in synchronized cells inhibits cell cycle reentry and the phosphorylation of the retinoblastoma protein (Rb), whereas in exponentially growing cells, HIN-1 induces apoptosis without apparent cell cycle arrest and effect on Rb phosphorylation. Investigation of multiple signaling pathways revealed that mitogen-induced phosphorylation and activation of AKT are inhibited in HIN-1-expressing cells. In addition, expression of constitutively activate AKT abrogates HIN-1-mediated growth arrest. Taken together, these studies provide further evidence that HIN-1 possesses tumor suppressor functions, and that these activities may be mediated through the AKT signaling pathway.

Apoptosis↗