Mesmo gene tem efeitos opostos em homens e mulheres

Gene AR (receptor de andrógeno) funciona de forma diferente em homens e mulheres, desempenhando papéis opostos no câncer de mama e no câncer de próstata.

Gene com efeitos opostos

Pesquisadores norte-americanos descobriram que um gene - conhecido como receptor de andrógeno (AR) - está associado tanto com o câncer de próstata quanto com o câncer de mama.

Contudo, eles verificaram que este mesmo gene tem efeitos opostos nas duas doenças.

No câncer de próstata, o AR promove o crescimento do câncer quando o gene está "ligado".

No câncer de mama, o AR promove o crescimento do câncer quando o gene está "desligado", como acontece frequentemente após a menopausa, quando cessa a produção AR nas mulheres.

Gene com gênero

A pesquisa não apenas revela que ação do gene é diferente entre homens e mulheres, como também mostra a dificuldade de utilização das descobertas genéticas sem um acompanhamento muito cuidadoso dos efeitos gerais de cada gene.

É por isto que cada vez mais os cientistas se recusam a falar em "gene disso" ou "gene daquilo".

Esta nova pesquisa, por exemplo, demonstra que o tratamento do câncer de próstata e do câncer de mama exigem abordagens completamente opostas em relação a um mesmo gene.

No tratamento do câncer de próstata, a estratégia deve ser bloquear o AR; já no câncer de mama a estratégia deve ser a de apoiar a produção do AR.

Brócolis e vinho tinto

Os pesquisadores se concentraram em saber se a molécula do receptor de andrógeno (AR) dá algum indício de uma proteína supressora de tumores chamada PTEN.

Já se demonstrou um forte efeito da PTEN, por exemplo, no combate ao câncer de próstata pela ação do sulforafano, um composto presente nosbrócolis.

• Explicado efeito do brócolis contra o câncer de próstata

A PTEN também está envolvida na ação anticâncer dos polifenóis presentes no vinho tinto.

• Vinho tinto e chá verde interrompem câncer de próstata

A pesquisa descobriu que o AR inibe a expressão da PTEN em células do câncer de próstata, mas estimula a expressão da PTEN em células do câncer de mama.

Isto explica porque a progressão do câncer de próstata está associada com a expressão aumentada do AR - uma estratégia comum de tratamento do câncer de próstata envolve bloquear o AR.

Por outro lado, a maioria dos cânceres de mama ocorrem no período pós-menopausa, após a cessação da produção de AR - a suplementação de AR é uma estratégia para o tratamento do câncer de mama.

Tratamento personalizado por sexo

Os cientistas concluíram que o comportamento conflitante do gene exige que se façam novas pesquisas para identificação de co-fatores que possam explicar esse comportamento e auxiliar no diagnóstico e no tratamento das duas doenças.

"Nossas observações ajudam a explicar porque o risco do câncer de próstata pode ser reduzido pela metade bebendo-se vinho tinto, que aumenta a expressão da PTEN," escrevem Charis Eng, Robert Silverman e Warren Heston, autores do estudo.

"Nossos dados também sugerem que o tratamento do mesmo câncer deve ser personalizado para homens e para mulheres," concluem eles.

O trabalho foi publicado na revista Oncogene.

Bridging the Gap: Neuroscientists Find Normal Brain Communication in People Who Lack Connections Between Right and Left Hemispheres

ScienceDaily (Oct. 19, 2011) — Like a bridge that spans a river to connect two major metropolises, the corpus callosum is the main conduit for information flowing between the left and right hemispheres of our brains. Now, neuroscientists at the California Institute of Technology (Caltech) have found that people who are born without that link -- a condition called agenesis of the corpus callosum, or AgCC -- still show remarkably normal communication across the gap between the two halves of their brains.

Top image: Magnetic resonance images comparing a healthy subject (left) with an AgCC patient (right). The corpus callosum is the thick, 'c'-shaped structure outlined in the healthy brain and missing from the AgCC brain. Bottom image: Functional magnetic resonance images highlight symmetric patterns of synchronized activity in both healthy (left) and AgCC subjects (right) during rest with eyes closed. More than 15 of this type of network were found to be preserved in AgCC subjects. 

Their findings are outlined in a paper published Oct. 19 in The Journal of Neuroscience.

Our brains are never truly at rest. Even when we daydream, there is a tremendous amount of communication happening between different areas in the brain. According to J. Michael Tyszka, lead author on the Journal of Neuroscience paper and associate director of the Caltech Brain Imaging Center, many areas of the brain display slowly varying patterns of activity that are similar to one another. The fact that these areas are synchronized has led many scientists to presume that they are all part of an interconnected network called a resting-state network. Much to their surprise, Tyszka and his team found that these resting-state networks look essentially normal in people with AgCC, despite the lack of connectivity.

"This was a real surprise," says Tyszka. "We expected to see a lot less coupling between the left and right brain in this group -- after all, they are missing about 200 million connections that would normally be there. How do they manage to have normal communication between the left and right sides of the brain without the corpus callosum?"

The work used functional magnetic resonance imaging (fMRI) to demonstrate that synchronized activity between the left and right brain survives even this sort of radical rewiring of the nerve connections between the two hemispheres. The presence of symmetric patterns of activity in individuals born without a corpus callosum highlights the brain's remarkable plasticity and ability to compensate, says coauthor Lynn Paul, research staff member and lecturer in psychology at Caltech. "It develops these fundamental networks even when the left and right hemispheres are structurally disconnected."

The study that found the robust networks is part of an ongoing research program led by Paul, who has been studying AgCC for several decades. AgCC occurs in approximately one of every 4000 live births. The typical corpus callosum comprises almost 200 million axons -- the connections between brain cells -- and is the largest fiber bundle in the human brain. In AgCC, those fibers fail to cross the gap between the hemispheres during fetal development, forcing the two halves of the brain to communicate using more indirect and currently unknown means.

"In the 1960s and 1970s, Roger Sperry at Caltech studied 'split-brain' patients in whom the corpus callosum was surgically severed as a treatment for epilepsy," explains Paul. "Our research on AgCC has moved in a different direction and focuses on a naturally occurring brain malformation that occurs before birth. This allows us to examine how, and to what extent, the brain can compensate for the loss of the corpus callosum as a person grows to adulthood."

According to the team, the findings are especially valuable in light of current theories that link impaired brain connections with clinical conditions including autism and schizophrenia.

"We are now examining AgCC subjects who are also on the autism spectrum, in order to gain insights about the role of brain connectivity in autism, as well as in healthy social interactions," says Tyszka. "About a third of people with AgCC also have autism, and altered connectivity in the corpus callosum has been found in autism. The remarkable compensation in brain functional networks that we found here may thus have important implications also for understanding the function of the brains of people with autism."

The work in the paper, "Intact bilateral resting-state networks in the absence of the corpus callosum," was carried out in the laboratory of Ralph Adolphs, Bren Professor of Psychology and Neuroscience at Caltech, with the help of postdoctoral scholar Daniel Kennedy. It was supported by funding from the Gustavus and Louise Pfeiffer Research Foundation, the Simons Foundation, the National Institute of Mental Health, and the National Alliance for Research on Schizophrenia and Depression.