ABSTRACT
The serine/threonine kinase Akt is frequently activated in human cancers and is considered an attractive therapeutic target. However, the relative contributions of the different Akt isoforms to tumorigenesis, and the effect of their deficiencies on cancer development are not well understood. We had previously shown that Akt1 deficiency is sufficient to markedly reduce the incidence of tumors in Pten(+/-) mice. Particularly, Akt1 deficiency inhibits endometrial carcinoma and prostate neoplasia in Pten(+/-) mice. Here, we analyzed the effect of Akt2 deficiency on the incidence of tumors in Pten(+/-) mice. Relative to Akt1, Akt2 deficiency had little-to-no effect on the incidence of prostate neoplasia, endometrial carcinoma, intestinal polyps and adrenal lesions in Pten(+/-) mice. However, Akt2 deficiency significantly decreased the incidence of thyroid tumors in Pten(+/-), which correlates with the relatively high level of Akt2 expression in the thyroid. Thus, unlike Akt1 deletion, Akt2 deletion is not sufficient to markedly inhibit tumorigenesis in Pten(+/-) mice in most tested tissues. The relatively small effect of Akt2 deletion on the inhibition of tumorigenesis in Pten(+/-) mice could be explained, in part, by an insufficient decrease in total Akt activity, due to the relatively lower Akt2 versus Akt1 expression, and relatively high blood insulin levels in Pten(+/-)Akt2(-/-) mice. The relatively high blood insulin levels in Pten(+/-)Akt2(-/-) mice may elevate the activity of Akt1, and possibly Akt3, thus, limiting the reduction of total Akt activity and preventing this activity from dropping to a threshold level required to inhibit tumorigenesis.
Subject(s)
Neoplasms, Experimental/etiology , PTEN Phosphohydrolase/physiology , Proto-Oncogene Proteins c-akt/physiology , Adrenal Gland Neoplasms/etiology , Animals , Endometrial Neoplasms/etiology , Female , Insulin/blood , Male , Mice , Mice, Inbred C57BL , Neoplasms, Experimental/prevention & control , Prostatic Intraepithelial Neoplasia/etiology , Prostatic Neoplasms/etiology , Proto-Oncogene Proteins c-akt/deficiency , Thyroid Neoplasms/etiologyABSTRACT
OBJECTIVE: To survey Human Papilloma Virus (HPV) infection in Chinese Women of Jiangsu Province and discuss the relationship between HPV and the biology of cervical cancer. METHODS: Two thousand, one hundred and fifty-three sexually active women (including 66 cases of cervical cancer) were selected for high-risk human papilloma virus DNA test with Hybrid Capture II (HCII). RESULTS: The overall HPV prevalence was 32.6% (701/2153) with higher positive rates in cervical carcinoma and Cervical Interstitial Neoplasia (CIN) [93.9% and 54.6%] respectively. For women aged 40-59 years, the overall high-risk HPV prevalence was higher than those of other age groups. Compared with CIN I, the positivity rate and viral load of HPV DNA in CIN III is much higher (80.2% vs 29.9%, 11.89 vs 0.53). Ninety-four per cent (64/66) of patients with Cervical cancer were detected to be HPV positive. There was no significant difference in HPV DNA among each clinical stage and pathologic grade. But the positive rates and the value of HPV DNA were higher in the patients with cervical interstitial incursion. Eighty per cent of patients (20/25) could become negative within six months after operation. CONCLUSIONS: High-risk HPV DNA test is effective in screening for cervical diseases. HC II is an effective method to detect HPV DNA.
OBJETIVO: Investigar la infección por el virus del papiloma humano (VPH) en las mujeres chinas de la Provincia de Jiangsu y analizar la relación entre VPH y la biología del cáncer cervical o del cuello uterino. MÉTODOS: Dos mil ciento cincuenta y tres mujeres sexualmente activas (incluyendo 66 casos de cáncer cervical) fueron seleccionadas para una prueba de ADN con el fin de detectar el virus del papiloma humano de alto riesgo mediante Captura Híbrida 2 (HC2). RESULTADOS: La prevalencia general de VPH fue 32.6% (701/2153), hallándose las tasas positivas más altas en el carcinoma cervical y la neoplasia intersticial cervical (NIC) [93.9% y 54.6%]. Para las mujeres de 40-59 años de edad, la prevalencia general de VPH de alto riesgo fue mayor que para los otros grupos etarios. En comparación con el CIN, la tasa de positividad y la carga viral de ADN del VPH en el CIN es mucho mayor (80.2% vs 29.9%, 11.89 vs 0.53). Se detectó que noventa y cuatro por ciento (64/66) de las pacientes con cáncer del cuello uterino eran VPH positivas. No hubo ninguna diferencia significativa en el ADN del VPH ADN entre cada fase clínica y el grado patológico. No obstante, tanto las tasas positivas como el valor de VPH ADN fueron más altos en las pacientes con incursión intersticial cervical. Ochenta por ciento de las pacientes (20/25) podrían volverse negativas en seis meses tras la operación. CONCLUSIONES: La prueba de ADN para la detección del virus del papiloma humano de alto riesgo es un medio efectivo para el tamizaje de las enfermedades cervicales. El HC2 es un método efectivo para detectar el ADN del VPH.
